Cmbm Exam Ii

Front 1

General Carbohydrate Metabolism

Back 1

CHO-->Glucose-->Glycolysis-->Acetyl CoA-->TCA-->Oxidative Phosphorylation

Front 2

General Fatty Acid Metabolism

Back 2

FAs-->Acetyl CoA-->TCA
-->Oxidative Phosphorylation

Front 3

General Protein Metabolism

Back 3

Proteins-->AAs-->TCA--> Oxidative Phosphorylation

Front 4

Glycolysis

Back 4

Occurs in Oxygen depletion. Creates less ATP than OXPHOS

Front 5

FA Usage

Back 5

Not used by brain. First priority for Muscle. If FFA are very available to muscle, glycolysis decreases.

Front 6

Keto Acids Usage

Back 6

First priority for brain. Not used by muscle unless FA unavailable

Front 7

Glucose Usage

Back 7

Used most of the time (due to Keto Acid scarcity) in Brain. Used in muscle only if FA and Keto acids are unavailable.

Front 8

Fuel Storage

Back 8

Stores(days/months)
Meals (hours)
Blood(minutes)
ATP(seconds)

Front 9

Fuel storage CHO

Back 9

CHO-->Glucose-->Glycogen (liver and muscles)

Front 10

Fuel Storage Proteins

Back 10

Proteins-->AAs-->muscle (and other proteins)

Front 11

Fats Storage

Back 11

Fats-->FAs-->Triglycerides--> Adipose tissue

Front 12

CHO as Energy Source

Back 12

Largest portion of dietary calories but one mole glucose yields only 34-36 ATP

Front 13

Fats as energy source

Back 13

Most efficient fuel. One mole palmitate yields 129 ATP

Front 14

Fuel sparing during starvation

Back 14

Glucose is needed for brain and RBC.
Protein is needed to sustain body function.
Fat storage makes FAs available to sustain.

Front 15

Protein Sparing

Back 15

During Prolonged Fast.
First, glycogen used. Then Protein metabolism reaches peak in 12 hours. However, after this point, less protein is metabolized and more FFA are metabolized. Tend to retain stored fat until needed in starvation

Front 16

Cell Membrane glucose transporters

Back 16

Glycolysis requires glucose to enter cell membrane through transporters. Insulinm determines availability of transporters at cell plasma membrane.

Front 17

FA and GLucose Metabolism

Back 17

Share same endpoint (Acetyl CoA) so if excess FA there will be excess Acetyl CoA and glycolysis will shut down.

Front 18

Metabolic Syndrome

Back 18

One or more of:
Type II diabetes
Impaired Glucose tolerance
Insulin resistance

+

Two or more of:
Hypertension
Obesity
Hypertricglyceremia
Low HDL
Microalbuminuria

with often cooccuring:
Hyperuricemia
Hypercoagulability
Hyperleptinemia

yields Metabolic Syndrome

leads to Diabetes, HIgh BP, Heart Disease, Stroke, Coagulopathies, Kidney Disease

Front 19

Quercetin

Back 19

Flavonoid found in apple skins, berries, red wine, etc.
Helped mice run more by creating more mitochondria.
FRS develops quercetin sports drink.
Drink improves high intensity performance.
Lance armstrong promotes
No difference between placebo and Quercitin.

Market Research is done to find "antidotes" to problems.

Front 20

Inborn errors of metabolism

Back 20

Homocysteinuria
Phenylketonuria
Tay-Sachs disease
Maple Syrup Urine disease
Tyrosinemia
Gaucher's Disease
Niemann-Pick disease
Fabry's disease
Glycogen storage diseases
Galactosemia
Hereditary Fructose Intolerance

Front 21

Metabolic Diseases of Muscle

Back 21

Acid Maltase Deficiency(Pompe's disease)
Carnitine Deficiency
Carnitine Palmityl Transferase Deficiency
Debraucher Enzyme Deficiency
Lactate Dehydrogenase Deficiency
Myoadenylate Deaminase Deficiency
Mitochondrial Myopathy
Phosphofructokinase Deficiency
Phosphoglycerate Kinase Deficiency
Phosphoglycerate mutase deficiency
phosphorylase deficiency (McArdle's Disease)

Front 22

Ratios of AMP/ADP/ATP

Back 22

In liver vs muscle same ADP and AMP but ATP 3.0 in liver and 5.0 in muscle

Front 23

anemia or ischemia

Back 23

limits Oxygen delivery necessary for efficient fuel utilization

Front 24

CHO processed into Glucose

Back 24

all for circulation

Front 25

FAs to Ketone Bodies

Back 25

more easily transported around body (h20 soluble)

Front 26

Glycerol, lactate, pyruvate

Back 26

3 carbon intermediate molecule
glycerol is backbone to FA
lactate and pyruvate come from FA metabolism

Front 27

Ethanol

Back 27

2 carbon fuel
only used when built into FA

Front 28

Places TCA cycle occurs

Back 28

Liver
Adipose
Muscle
Brain
(not RBC)

Front 29

Places B-oxidation occurs

Back 29

Liver
Muscle
(not Adipose, Brain, RBC)

Front 30

Places Ketone Bodies Form

Back 30

Liver
nowhere else

Front 31

Places Ketone Bodies Used

Back 31

Some Adipose
Muscle
Brain (when starved)
(no rbc, no liver, no brain when free glucose)

Front 32

Place of Lipogenesis

Back 32

Liver
Some adipose

Front 33

place of gluconeogenesis

Back 33

Liver
nowhere else

Front 34

places of Glycogen metabolism

Back 34

Liver
Muscle
Some adipose
Brain (sometimes)
(no RBC)

Front 35

Lactate formed

Back 35

Muscle during exercise
RBC
(A little in brain, adipose, liver)

Front 36

B-Oxidation

Back 36

break up long chain FAs into 2-carbon pieces
ketone bodies are end products of FA metabolism
FAs not H20 soluble and dont transport across body well
Ketone Bodies do

Front 37

Lipogenesis

Back 37

make FAs out of excess fuel

Front 38

Gluconeogenesis

Back 38

processes glucose partway
produces glucose when a tissue needs it

Front 39

Glycogen

Back 39

storage form of CHO

Front 40

Lactate

Back 40

last step in glycolysis
not usually used because products of glycolysis are taken into TCA
if theres is low oxygen, lactate increases glycolysis
muscle is primary lacatate formation site because energy demands are high and oxygen is not supplied fast enough

Front 41

Lipogenesis

Back 41

make FAs out of excess fuel

Front 42

Gluconeogenesis

Back 42

processes glucose partway
produces glucose when a tissue needs it

Front 43

Glycogen

Back 43

storage form of CHO

Front 44

Lactate

Back 44

last step in glycolysis
not usually used because products of glycolysis are taken into TCA
if theres is low oxygen, lactate increases glycolysis
muscle is primary lacatate formation site because energy demands are high and oxygen is not supplied fast enough

Front 45

Liver Energy

Back 45

Uses everything but ketone bodies

Front 46

Muscle energy

Back 46

uses fat,ketone bodies, glycogen

Front 47

RBC energy

Back 47

uses glucose, processes it into lactate

Front 48

Glycolysis decreases

Back 48

as FFA become available
Glucose-6-Phosphate is first step in metabolizing glucose
Amount of G-6-P indicates level of glycolysis
FFA decrease, More G-6-P available
FFA increase, less G-6-P

Front 49

CHO Pathway

Back 49

CHO-->glucose--> either metabolism (glycolysis) or glycogen(storage)-->liver and muscles

Front 50

Proteins Pathway

Back 50

Proteins-->AAs--> MUscle(and other proteins) (no specific form of protein storage)

Front 51

Fats Pathway

Back 51

Fats-->FAs-->Triglycerides--> adipose

Front 52

CHO Pathway Alternate

Back 52

CHO-->glucose-->Acetyle CoA--> FAs-->triglycerides-->adipose

Front 53

Stored fuels

Back 53

adipose triglycerides>protein>glycogen

Front 54

Circulating fuels

Back 54

glucose>triglycerides>FFA

Front 55

3 Effects FFA on Normal Cell

Back 55

Decrease number of glucose transporters that come to surface and affect function of glucose transporters
decrease glucose transform to glycogen
decrease glucose metabolism

Front 56

Kwashiorkor

Back 56

Starvation
excceded capacity to using AAs via breaking down proteins\body makes use of fat (until no more fat, then make use of proteins)
liver cant produce enough albumin which functions to maintain fluid inside bloodstream
tissues are leaking and fluid collects in body cavities
patient presents with swollen belly and stiff arms/legs

Front 57

Type II diabetes

Back 57

Hyperglycemia: impaired glucose tolerance following a glucose load so glucose isnt going where it is supposed to
usually accompanied by insulin resistance
associated with obesity
possible mechanisms:
fewer receptors, dysfunctional receptors, aberrant signaling, fewer or occluded glucose transporters

Front 58

ketogenic diet

Back 58

helps epilepsy

Front 59

Metabolic diseases

Back 59

mostly autosomal recessive

Front 60

Homocysteinuria

Back 60

inability to process homocysteine
builds up in blood stream
promotes clotting
pectus excavatum is a marker
children affected in utero are born with osteoporosis

Front 61

Phenylketonuria

Back 61

phenylalanine hydroxylase that takes OH group that puts ring structure on tyrosine doesnt function properly
phenylalanine builds up, neurons function poorly

Front 62

Tay Sachs Disease

Back 62

prevalent in jews of eastern european descent
defect in processing glycolipid that is prevalent in brain cells and it builds up
children develop normally then regress and death is inevitable

Front 63

Mitochondria

Back 63

outermost membrane is porous
inner membrane is thick and folded (cristae)
holds proton gradient to use as energy
cristae are studded with proteins for oxidative phosphorylation
enzymes for TCA cycle are in matrix

Front 64

Mitochondrial Myopathies

Back 64

Cause energy defects

Front 65

Reproductive Hormones

Back 65

testosterone
progesterone
estradiol
androgen
prolactin

Front 66

Growth and Development Hormones

Back 66

GH
TH
Cortisol
Growth Factors
Prolactin

Front 67

Homeostatic Hormones

Back 67

Aldosterone
VAsopressin
Vitamin D
Retinoic Acid (vitamin A)

Front 68

Energy Production, utilization, storage

Back 68

insulin
glucagon
epinephrine
cortisol
leptin

Front 69

RBC and Brain Metabolic Interactions

Back 69

most fastidious and voracious organ needs constant glucose supply

Front 70

Heart metabolic needs

Back 70

FAs, lactate, ketone bodies

Front 71

Muscle Metabolic Needs

Back 71

FLEXIBLE
FAs major fuel source at rest
Glucose from glycogen store is used @ earlier stage of exertion then FAs as dominant fuel

Front 72

Liver metabolic needs

Back 72

Most flexible
Plays major role in keeping stable blood glucose level

Front 73

Intestine

Back 73

digestion/absorption of nutrients

Front 74

Blood

Back 74

superhighway for balance/transportation of nutrients

Front 75

pathway of circulation

Back 75

pathway

Front 76

Exocrine Pancreas

Back 76

Trypsinogen
Chymotrypsinogen
Pancreatic Lipase
Amylase

Front 77

Endocrine Pancreas

Back 77

insulin (B cells)
glucagon (a cells)
gastrin (Delta cells)
pancreatic polypeptide (F cells)

Front 78

islet of langerhans

Back 78

B cells in core
other cells mixed in mantle

Front 79

Insulin formation

Back 79

preproinsulin-->proinsulin--> insulin
C-peptide is secreted with insulin (useful for diagnosis)
interspecies insulin are similar

Front 80

Insulin formation

Back 80

preproinsulin is secreted as random coil on membrane associated ribosomes with leader sequence--(assists with membrane transport)
leader sequence is cleaved after membrane transport
resultant proinsulin folds into stable confirmation
disulfide bonds form between alpha and beta chains
connecting sequence connects alpha and beta chains and when cleaved alpha+beta chains+ disulfide bonds become a mature insulin molecule

Front 81

Insulin formation steps

Back 81

1. nucleus (produce mRNA for preproinsulin production)
2. granular ER (synthesis of preproinsulin, which is cleaved by microsomal enzymes into proinsulin
3. Transfer vesicles to Golgi
4. Golgi (package, convert proinsulin to insulin)
5. Glucose into mitochondria, influx Ca++
6. Secretory granules of insulin condense and are released

Front 82

Regulation of insulin step one

Back 82

1. Glucose transporter 2 (GLUT2) is specific to liver and pancreas
responsible for glucose absorption
senses blood glucose levels
mediates transportation of glucose to B cells

Front 83

Regulation of insulin step two

Back 83

increase glucose catabolism/atp synthesis

Front 84

regulation of insulin step three

Back 84

close K+ channels/open Ca++ channels

Front 85

regulation of insulin step 4

Back 85

Ca++ influx

Front 86

regulation of insulin step 5

Back 86

insulin synthesis/secretion

Front 87

insulin signaling pathways for muscle and adipose tissue

Back 87

Glucose transporter 4 (GLUT4) located in cytoplasm
translocates to plasma membrane with insulin stimulation

Front 88

insulin signaling pathways

Back 88

1. insulin binds to insulin receptor
2. autophosphorylation of tyrosine on B subunits
3. phosphorylation of IRS (insulin receptor substrate)
4. GLUT4 translocates to Plasma membrane
5. Glucose influx
6. glycolysis
7. glycogen synthesis
8. FA synthesis

Front 89

Insulin effects on liver 1

Back 89

increase glucose phosphorylation

Hint 89

affects glucokinase

Front 90

insulin effects on liver 2

Back 90

increase glycolysis

Hint 90

affects phosphofructokinase-1, pyruvate kinase

Front 91

insulin effects on liver 3

Back 91

increased glycogen synthesis

Hint 91

affects glycogen synthase

Front 92

insulin effects on liver 4

Back 92

increased FA synthesis

Hint 92

Affects AcetylCoA Carboxylase, ATP Citrate Lyase, Malic Enzymes

Front 93

Insulin effects on liver 5

Back 93

decreased gluconeogenesis

Hint 93

affects PEP carboxykinase, F-1,6-Bisphosphatase, Glucose-6-Phosphatase

Front 94

insulin effects on liver 6

Back 94

decreased glycogenolysis

Hint 94

affects glycogen phopshorylase

Front 95

insulin effects on liver 7

Back 95

increase pentose phosphate pathway

Hint 95

affects G-6-P dehydrogenase

Front 96

insulin effects on adipose 1

Back 96

increased glucose uptake

Hint 96

affects glucose carrier

Front 97

insulin effects on adipose 2

Back 97

increased glycolysis

Hint 97

affects phosphofructokinase-1

Front 98

insulin effects on adipose 3

Back 98

increased pentose phosphate pathway

Hint 98

affects Glucose-6-Phosphate Dehydrogenase

Front 99

insulin effects on adipose 4

Back 99

Increased Pyruvate Oxidation

Hint 99

affects pyruvate dehydrogenase

Front 100

insulin effects on adipose 5

Back 100

increased triglyceride utilization

Hint 100

affects lipoprotein lipase

Front 101

insulin effects on adipose 6

Back 101

increased triglyceride synthesis

Hint 101

affects glycero-3-phosphate acyl transferase

Front 102

insulin effects on adipose 7

Back 102

decreased lipolysis

Hint 102

affects hormone sensitive lipase

Front 103

insulin effects on skeletal muscle

Back 103

increased glucose uptake

Hint 103

affects glucose carrier

Front 104

insulin effects on skeletal muscle

Back 104

increased glycolysis

Hint 104

affects phosphofructokinase-1

Front 105

insulin effects on skeletal muscle

Back 105

increased glycogen synthesis

Hint 105

affects glycogen synthase

Front 106

insulin effects on skeletal muscle

Back 106

decreased glycogenolysis

Hint 106

affects glycogen phosphorylase

Front 107

insulin effects on skeletal muscle

Back 107

increased protein synthesis

Hint 107

affects translation initiation complex

Front 108

Biochemical affects of insulin

Back 108

increased cell permeability to glucose (muscle and adipose)
increased glycolysis
increased glycogen synthesis
increased triacylglycerol synthesis
decreased gluconeogenesis
decreased lipolysis
decreased protein degradation
increased protein, DNA, RNA synthesis

Front 109

Physiological affects of insulin

Back 109

signals fed state
decreased blood glucose level
increased fuel storage
increased cell growth and differentiation

Front 110

Glucagon

Back 110

synthesized in alpha cells in pancreas
preproglucagon-->proglucagon--> glucagon
single chain 29 polypeptides
secretion is inhibited by glucose and insulin
increased secretion stimulated by: AAs, catecholamines, glucocorticoids, nervous system

Front 111

receptor mediated activation of PKA

Back 111

1 molecule glucagon-->
~20 G-Proteins-->
~100 cAMP-->
~100-1000 phosphorylations-->
net effect~10^5, 10^6

Front 112

Glucagon effects on blood glucose levels

Back 112

glucose decreased, then glucagon increases, cAMP increases, PKA increases

increased PKA leads to increased phosphorylase--> increased glycogenolysis--> increased glucose

increased PKA leads to decreased glycogen synthase--> decreased glycogen synthesis --> increased glucose

increased PKA leads to decreased pyruvate kinase--> increased gluconeogensis--> increased glucose

increased PKA leads to decreased PFK2, increased F2,6BPase--> decreased F2,6BP--> decreased glycolysis--> increased glucose

Front 113

glucagon increases

Back 113

increases glucagon/glucagon receptor--> increased cAMP--> increased PKA--> increased phosphorylation-->decreased glycogen synthase--> decreased glycogen synthesis -->increased glycogen phosphorylase--> increase glycogen degradation--> increased glucose

Front 114

decreased glycolysis

Back 114

affects
glucokinase (induction/repression)
PFK1 (other)
Pyruvate Kinase (induction/repression)

Front 115

Increased gluconeogenesis

Back 115

affects
PEP carboxylase (induction/repression)
Fructose 1,6 bisphosphatase (induction/repression, other)
glucose-6-phosphatase (induction/repression)

Front 116

decreased glycogen synthesis

Back 116

affects glycogen synthase (phosphorylation)

Front 117

increased glycogenolysis

Back 117

affects glycogen phosphorylase (phosphorylation)

Front 118

decreased FA synthesis

Back 118

affects AcetylCoA carboxylase (induction/repression) (phosphorylation)

Front 119

increased FA oxidation

Back 119

affects carnitine palmityl transferase-1 (induction/repression)

Front 120

High CHO meal

Back 120

increased insulin, decreased glucagon

Fructose-6-P --> Fructose 2,6-P phosphorylated by PFK2

Front 121

Fasting

Back 121

decreased insulin, increased glucagon

fructose 2,6-p-->Fructose-6-P dephosphorylated byF-2,6BPase

Front 122

Glucose metabolism

Back 122

Glucose--> Fructose-6-Phosphate

fructose-6-phosphate + PFK1(from F2,6BP)--> Fructose 1,6 BP--> 2 pyruvates

Fructose 1,6 Bisphosphate +F-1,6-BPase(from F 2,6BP)--> Fructose-6-Phosphate

Front 123

type I diabetes

Back 123

childhood, thin, decreased insulin, increased glucagon, increased gluconeogenesis, increased blood glucose

insulin is remedy
10% cases

Front 124

Type II diabetes

Back 124

adolescence, obese, 90% cases

insulin receptor downregulation
glucagon is similar
nutrient usage is down
increase in blood glucose/cholesterol/FA

treat with exercise and dietary modifications

Front 125

catecholamines neurotransmitter

Back 125

DOPA
dopamine

Front 126

catecholamines hormone

Back 126

Norepinephrine (transmitter)
Epinephrine

Front 127

tyrosine anabolism

Back 127

tyrosine + tyrosine hydroxylase (rate lmiting) --> DOPA + DOPA decarboxylase--> Dopamine + Dopamine hydroxylase--> Norepinephrine + Norepinephrine n-methyltransferase--> Epinephrine

Front 128

synthesis in adrenal medulla

Back 128

physical exertion/psychological stress/cold---> anterior pituitary

hypothalamus--> anterior pituitary (catecholamine releasing)--> adrenal medulla

Front 129

signal transduction of B2 receptors

Back 129

identical to glucagon receptor
Activate adenylate cyclase--> increas in cAMP--> activate PKA

Front 130

catecholamines

Back 130

slows down gut
speeds up heart
increase sweating
mobilize stores of energy

Front 131

epinephrine effect on liver

Back 131

Increase EPI--> adrenergic receptor--> increase cAMP--> increase in PKA-->

increase gluconeogenesis
decrease glycolysis
increased glycogenolysis
decrease glycogenesis

-->

increase blood glucose

opposite effect of epi on heart muscle vs liver

Front 132

heart

Back 132

heart

Front 133

effect of epi on adipose

Back 133

increase lipolysis
hormone sensitive lipase

Front 134

effect of epi on adipose

Back 134

decreased triglyceride utilization
lipoprotein lipase

Front 135

effect of epi on liver

Back 135

decreased glycolysis
phosphofructokinase-1

Front 136

effect of epi on liver

Back 136

increased gluconeogenesis
fructose-1,6-bisphosphatase

Front 137

effect of epi on liver

Back 137

decreased glycogen synthesis
glycogen synthase

Front 138

effect of epi on liver

Back 138

increased glycogenolysis
glycogen phosphorylase

Front 139

effect of epi on liver

Back 139

decreased FA synthesis
lipoprotein lipase

Front 140

effect of epi on heart

Back 140

increased glycolysis
phosphofructokinase-1

Front 141

effect of epi on heart

Back 141

decreased glycogen synthesis
glycogen synthase

Front 142

effect of epi on heart

Back 142

increased glycogenolysis
glycogen phosphorylase

Front 143

effect of epi on heart

Back 143

increased triglyceride utilization
lipoprotein lipase

Front 144

cortisol/glucocorticoids

Back 144

chronic stress--> corticotropin releasing factor (CTRF) from hypothalamus--> ACTH (adrenocorticotropic hormone) from anterior pituitary gland--> cortisol and glucocorticoids (from adrenal cortex)--> glucocorticoid receptor--> gene expression -->long term--> increased lipolysis, increased protein degradation, increased gluconeogenesis

Front 145

Cortisol/Glucocorticoids Effects Adipose

Back 145

Increase Lipolysis
affects hormone sensitive lipase

Front 146

Cortisol/Glucocorticoids Effects muscle

Back 146

Increase protein degradation

Front 147

Cortisol/Glucocorticoids Effects liver

Back 147

increase glycogen synthesis, increased gluconeogenesis
affects glycogen synthase
enzymes in amino acid metabolism
PEP carboxykinase

Front 148

Low Blood Glucose Cascade

Back 148

LBG-->Pancreas (A cells)--> glucagon

LBG-->Hypothalmic regulatory center-->ANS-->norepi
ANS--> adrenal medulla--> EPI

LBG-->hypothalmic regulatory center-->pituitary-->ACTH--> Adrenal cortex--> cortisol

Front 149

Leptin

Back 149

16kDa peptide hormone from adipocyte. amount proportional to bodyfat

+ leptin=when need tolose weight
- leptin=when need to gain weight

function to decrease food intake (satiety) and increase energy expenditure (metabolism)

Front 150

Db (leptin receptor)

Back 150

membrane protein enriched in hypothalamus. Coded for by Db gene (diabetes gene). Without this gene, no receptors, and become fat

Front 151

parabiosis

Back 151

circulatory systems of two mice joined together

Ob with normal-->lose weight
Db with normal--> normal lose wt
Ob with Db--> Ob lose wt

Front 152

leptin therapy

Back 152

used with people with leptin deficiency. no effect in those without deficiency

Front 153

orexigenic

Back 153

appetite stimulating
NPY producing
AgRP producing

GHRELIN (stomach)

Front 154

Anorexigenic

Back 154

Appetite suppressing
POMC producing
(a-MSH)

PYY intestine
CCK intestine
Leptin adipose
Insulin pancreas

Front 155

NPY

Back 155

neuropeptide Y

Front 156

AgRP

Back 156

Agouti-related peptide

Front 157

POMC

Back 157

propriomelanocortin

Front 158

a-MSH

Back 158

alpha melanocyte stimulating hormone

Front 159

Vitamin D and Vitamin A

Back 159

can penetrate cell membrane and act on receptor in nucleus

Front 160

Cortisol

Back 160

can penetrate cell membrane

Front 161

B-oxidation

Back 161

FAs precursors to acetyl coA and used to produce ketone bodies

Front 162

zymogens

Back 162

prevent digestion of pancreas itself

Front 163

pancreatic enzymes

Back 163

trypsinogen, chymotrypsinogen, pancreatic lipase, amylase

Front 164

Dela cells

Back 164

create gastrin and somatostatin

Front 165

F cells

Back 165

pancreatic polypeptides and inhibits somatostatin

Front 166

insulin

Back 166

signal peptide (lead strand) removed by signal peptidase

Front 167

procine or bovine insulin

Back 167

used in humans

Front 168

Glucose

Back 168

directly signals beta cells to release insulin

Front 169

GLUT2

Back 169

found in B cells, liver
senses blood glucose levels
enhances glucose influx
causes increased glycolysis and ATP synthesis
increased ATP closes K+ channels, K+ no longer flows into cell
indirectly opens CA++ channel
causes direct release of insulin (microfilaments contract in response to CA++ and will release vesicles of insulin into blood stream
CA++ binds to calmodulin--> transcription regulation of insulin through calcium response element binding protein

CREB + Ca++ has bound insulin gene promoter enabling transcription of insulin gene for next round of secretion

Front 170

Tetramer GLUT2

Back 170

four subunits (2 alpha, 2 beta
transciption of these subunits controlled by one promoter (so 1:1 ratio)

a-subunits extracellular and bind insulin
B subunits cross membrane
-c-terminus is in cytosol and equipped with tyrosine kinase activty
insulin binds receptor--> autophosphorylation of c-terminal B subunits--> phosphorylation of IRS--> glucose transporter recruited to plasma membrane

Front 171

GLUT4

Back 171

found in muscle and adipose tissue
normally located in cytosol
translocates to cell membrane with insulin stimulation
causes-glucose influx
catabolism
muscle glycogen made in muscle, FAs in adipocytes, stored as triacylglycerol

Front 172

glucagon

Back 172

inhibited by glucose/insulin
stimulated by AAs and their derivatives (arginine, alanine, GABA, catecholamines, glucocorticoids, GI hormones, increased FFA, nervous system control
carried to target tissue through bloodstream

G-protein coupled receptor

stimulation--> G-protein activation-->activate adenylate cyclase-->cAMP + PKA--> protein phosphorylation

PKA has catalytic and regulatory domains

cAMP binds to and removes regulatory domains

Front 173

GPCR

Back 173

G-protein coupled receptor uses GTP to make G-protein release GDP and bind a GTP

adenylate cyclase uses ATP to generate cAMP

requires 4 cAMP to fill regulatory domains of PKA because there are 2 domains with 2 binding sites each

phosphodiesterase turns cAMP into AMP to reduce cAMP concentration

-without cAMP, the regulatory domain of PKA will bind the catalytic domain to stop the reaction
strength of the signal depends on how many glucagon bind receptors and how high cAMP concentration gets

Front 174

glycolysis

Back 174

uses glucose to generate pyruvate and ATP (regulated by Fructose-2,6-Bisphosphate (f-2,6-BP) which activates PFK-1 and inhibits Fructose 1,6-Bisphosphatase (F-1,6-BPase) thereby inhibiting the reverse process

Front 175

PFK-2

Back 175

increases F-2,6-BP

Front 176

F-2,6-BPase

Back 176

decrease F-2,6-BP

Front 177

glucagon

Back 177

leads to phosphorylation, activates F-2,6-BPase

Front 178

insulin

Back 178

leads to dephosphorylation, activates PFK-2, PFK-1

Front 179

GLUT1 and GLUT 3

Back 179

RBC and Brain, high affinity, low capacity

Front 180

GLUT 2

Back 180

liver, pancreas, low affinity, high capacity

Front 181

GLUT4

Back 181

adipose and muscle (only if insulin is present)
increase glucose levels leads to glycosylation
-DNA, RNA, etc. glycosylation can modify transcription and translation of proteins
increased glucose all the time can be toxic
by having ttransporters, glucose is taken into cell in a way that is not toxic

Front 182

Catecholamine synthesis

Back 182

Tyrosine +tyrosine hydroxylase--> DOPA+dopamine decarboxylase (removes carboxyl group in form of CO2)--> Dopamine + domanine hydroxylase (with Vit C as a cofactor adds OH group)--> Norepinephrine +n-methyltransferase (adds methyl to NH2)--> epinephrine

Front 183

catecholamines

Back 183

work like glucagon but faster
in heart increases F-2,6-BP
in liver Decreases F-2,6-BP (want gluconeogenesis in liver)

Front 184

stress pathway

Back 184

stress-->hypothalamus--> CRF--> anterior pituitary--> ACTH--> adrenal cortex--> cortisol/glucocorticoids-->

lipolysis, gluconeogenesis, protein degradation

Front 185

leptin

Back 185

deletion of OB gene leads to obesity
Db knockout grows bigger than Ob knockout

Front 186

choleocystikinin

Back 186

released from small intestine during eating to promote sense of fullness and releasing of bile and digestive enzymes

Front 187

ATP Phosphate bonds

Back 187

gamma = high energy
B=less high
a=never used

Front 188

number of mitochondria

Back 188

depends on energy needs
~50% of cytoplasm of cardiac cells occupied by mitochondria
mature RBC has no mitochondria

Front 189

mitochondria

Back 189

outer permeable membrane
intermembrane space contains cytoplasm
inner membrane space is not permeable (including protons)
inner membrane folded into cristae (surface area)
inner membrane compartment called matrix

Front 190

mitochondrial matrix

Back 190

contains
TCA cycle enzymes
B oxidation
ATP synthase/ATP
ETC
Mitochondrial DNA

Front 191

B oxidation

Back 191

makes 2-carbon Acetyl CoA

Front 192

Complex

Back 192

group of functional units (protein)

Front 193

electron transport systems

Back 193

complexI-->coQ-->complexIII-->complexIV

complexII-->coQ-->complexIII-->complexIV

I and II merge through coQ

Front 194

proton pump efficiency

Back 194

10 protons pumped to intermembrane space when begin at complex I

6 when begin at complex II

Front 195

COmplex I

Back 195

NADH + H+ --> NAD+ (nadh is reducing equivalent)

Front 196

Complex II

Back 196

succinate-->fumarate

(TCA cycle has 8 steps/enzymes, but the only substrate on membrane of TCA cycle is succinate dehydrogenase) Complex II is not transmembrane

Front 197

protons pumped

Back 197

complex I-->4
complex II-->0
complex III-->2
Complex IV--> 4

Front 198

complex I

Back 198

>40 subunits
MW=1MDa
1 FMN (similar to FAD, extracts 2H from NADH to give to CoQ)
8 Fe-S clusters (accept e- from NADH), donate e- to Fe-S and then CoQ
Fe serves as a transport of electrons
Gaps b/t subunits form channel for proton pumping

alternate name (NADH dehydrogenase)

inactivated by rotenone, riboflavin deficiency

Front 199

complex II

Back 199

alt name: succinate dehydrogenase

has FAD and Fe-S

succinate donates e- to CoQ

inactivated by malonate

Front 200

complex III

Back 200

CoQ/CoEnzymeQ/Ubiquinone
-has CoQ
-NADH dehydrogenase donates electrons to bc1 complex
inactivated by generation of free radicals, doxorubicin

cytochrome bc1 complex
-ubiquinone-cytochrome c oxidoreductase
has Fe-S, Hemes (b562, c-1)

inactivated by antimysin, demerol, Fe deficiency

cytochrom c has Heme C

bc1complex donates e- to cytochrome oxidase
inactivated by Fe deficiency

Front 201

Complex IV

Back 201

cytochrome oxidase
complex IV
cytochrome AA3

has Heme-a

cytochrome c-->O2

inactivated by carbon monoxide, cyanide, ischemia, Fe and Cu deficiency (leads to Fe deficiency)

Carbon monoxide (binds to heme, blocks O2)

Front 202

Heme

Back 202

Fe molecule in center

Front 203

cyanide

Back 203

binds to heme Fe in complex IV prevents O2 from being used as a transporter and binding to heme

Front 204

general cycle

Back 204

AH2 (substrate) oxidized-->A + NAD+--> NADH

Fp(flavoprotein) +NADH--> FpH2 and NAD+

FpH2 + 2 Fe3+--> Fp + 2 Fe2+

2Fe2+ + 1/2 O2--> H20


1. reduced fuel passes electron to coenzyme
2. the electrons are passed from the coenzyme to a flavoprotein in a complex
3. the flavoprotein passes them to an iron containing cytochrome group
4. the last cytochrome passes them to oxygen, reducing it to water

Front 205

electrochemical potential

Back 205

cytosolic side has + charge (acidic), matrix side is - charge (basic) because of proton pump

driving force of ATP synthesis
a. electro-membrane potential
b. chemical-involves proton particles
c. electrochemical potential

Front 206

ATP synthase

Back 206

a protein complex
H+ channel
-Fo (C-subunits)

Catalytic Domain
-F1(a,b,a,b,y,d)

use the electrochemical potential to synthesize ATP

C-complex embeds in membrane
-flow of protons turns complex
-each c-subunit moves 30 degrees/proton. need 12H+ to turn 360 degrees

Y turns 360, 3 ATP synthesized

pool of protons inside the matrix are used for pumping

Front 207

oxidative phosphorylation

Back 207

complex I- FMN is main acceptor
complex II- FAD is main acceptor

Front 208

mitochondrial inner membrane transporters

Back 208

Adenosine Nucleotide Translocase (antiporter)
-ADP--> matrix
-ATP--> intermembrane space
charge difference gives process movement (electrochemical potential)

ATP synthase (uniport)
-H+--> matrix

Phosphate translocase
(symporter)
H2PO4--> matrix
H+--> matrix

concentration gives movement (chemical potential)

Front 209

mitochondria ATP synthesis

Back 209

oxidation of NADH or succinate
-electron passed to O2 through ETC to form H20
-formation of electrochemical potential
-potential used by ATP synthase to synthesize ATP
-oxidative phosphorylation
-oxidation and ATP synthesis

Front 210

different efficiencies of electron transfer chains

Back 210

complex I extracts elctrons from NADH and transfers them to complex III (and pumps 4H+)

complex II extracts electrons from succinate and passes them to complex III (no pump H+)

Electron transfer from complex III to complex IV pumps 2H+

Electron transfer from complex IV to O2 (pumps 4H+)

Front 211

ATP synthesized

Back 211

NADH oxidation pumps 10H+, synthesizes 2.5 ATP

FADH2 oxidation pumps 6H+ and synthesizes 1.5 ATP

Front 212

Vitamin B3 derivatives

Back 212

NAD+ (nicotinamide adenine dinucleotide)
NADP+ (nicotinamide adenine dinucleotide phosphate)

Front 213

Vitamin B3 deficiency

Back 213

glossitis (swollen tongue, inflamed)
pellagra (diarrhea, dermatitis, dementia)

B3 overdose is flushing

Front 214

Vitamin B2 derivatives

Back 214

FMN (flavin mononucleotide)
FAD (flavin adenine dinucleotide)

Front 215

Vitamin B2 deficiency

Back 215

cheilosis (inflamed lips, scaling/fissures at corner of mouth, glossitis)
corneal vascularization

Front 216

ATP synthesis and utilization

Back 216

Glucose, FAs, AAs--> acetyl CoA--> TCA cycle

FA is more efficient than glucose and proteins (more easily removed 2-carbon groups

Ketone bodies and Ethanol are energy enriched (easy to produce Acetyl CoA)

glucose-->pyruvate-->TCA-->FADH2 NADH-->ATP

Front 217

creatine phosphate

Back 217

energy can be stored temporarily as this

Front 218

Malate-Aspartate shuttle

Back 218

(antiporter)
two enzymes
-malate dehydrogenase
-aspartate aminotransferase
two transporters
-malate a-ketoglutarate
-glutamate aspartate transporter

H is transferred to oxaloacetate-->Malate which helps move NADH from cytosol into matrix by using a reducing equivalent)

(enzymes catalyze forward and backward reaction)

regenerates NADH

Front 219

glycerol-3-phosphate shuttle

Back 219

DHAP (dihydroxyacetone phosphate) + Glycerol-3-Phopshate dehydrogenase--> Glycerol-3-Phosphate

does not regenerate NADH--start at CoQ

Front 220

ATP in respiratory control

Back 220

"pulls" demand of O2 forward

Front 221

oligomycin inhibits ATP synthase

Back 221

binds to Fo of ATP synthase

blocks proton channel

inhibits atp synthesis

-lower atp, higher adp

etc is enhanced

increased electrochemical potential
ultimate ETS stops

keeps proton gradient intact

slows 02 consumption

Front 222

uncoupling phosphorylation from electron transport

DNP

Back 222

DNP (2,4 dinitrophenol) destroys H+ gradient allows continued ADP stimulation of 02 consumption without ATP synthesis

it is a weak acid/hydrophobic

DNP is protonated in the intermembrane space
protonated DNP diffuses into matrix
DNP is deprotonated in matrix
H+ gradient is disrupted
no ATP synthesized

Front 223

Thermogenin

Back 223

protein complex like DNP

oxidation of NADH/FADH
formation of H+ gradient
H+ gradient uncoupling by thermogenin
generation of heat
reducing ATP synthesis

Front 224

ADP

Back 224

required for ATP synthesis
atp hydrolysis controls ATP synthesis

ADP effects
-enhances oxidative phosphroylation
-increases rate of TCA cycle allosterically
-NADH is required for ATP synthesis
-NAD+ is required for TCA cycle

energy needs which consume NADH allow NAD+ to increase rate of TCA cycle

As energy needs decline, excess NADH slows down TCA cycle

rations of ATP/ADP and NADH/NAD control rate of activity

Front 225

interlocking regulation

Back 225

glycolysis
pyruvate oxidation
citric acid cycle
oxidative phosphorylation

all regulated by relative concentrations of
AMP
ADP
ATP
NAD
NADH

Front 226

calorie restriction/NADH/longevity

Back 226

CR seems to increase lifespan
during CR, Sirt1 (deacetylase) activity increases
NAD+ serves as Sirt1 activator
increased ratio NAD/NADH
lowers cholesterol, fasting glucose, blood pressure
slows aging, increases longevity


resveratrol
similar effects as CR without CR

Front 227

muscle work

Back 227

myosin heads engage with actin at multiple sites
myosin head has an ATP binding domain and is an ATPase
changes in myosin head conformation upon binding ATP, hydrolyzing ATP, or realeasing ADP allows contact with Actin and slide actin filament forward

ATP-releasing Y, B phosphate bonds provide energy

Front 228

Increase ATP

Increase ADP

Back 228

body has energy/body needs anergy

Front 229

1,3 Bisphosphoglycerate
Phosphoenol Pyruvate

Back 229

have PO4 bonds, high energy, that can be made into ATP

importnat in glycolysis, substrate level phosphorylation in RBC (no mitochondria)

Front 230

acetyl CoA

Back 230

all fuel ends up as acetyl CoA
has high energy ester bond

Front 231

creatine phosphate

Back 231

phosphate becomes sequestered
after big meal, some ATP is stored as creatine phosphate in muscles

releases more energy than just ATP

ATP lasts for 2 seconds, Creatine PO4 kicks in for 8 seconds, then muscle dips into glycogen

all high energy molecules can interconvert into ATP

also participate in energy requiring reactions

Front 232

energy carrier molecules

Back 232

NAD/NADH
NADP/NADPH
FAD/FADH2

Front 233

oxidative phosphorylation

Back 233

rxn by which ATP synthesis occurs

most efficient ATP reduction (O2 reduced)

Front 234

electrochemical gradient

Back 234

protonmotive force

Front 235

electron transport chain

Back 235

atp synthase (Fo/Fi ATPase)

Front 236

fuels used to produce reducing equivalent and ATp

Back 236

at substrate level phosphorylation

fuels being oxidized, O2 reduced to H20

Front 237

BMR

Back 237

weight in kg x 24

Front 238

brain's need for glucose is driving force in energy metabolism

Back 238

liver regulates the concentration of fuels in blood
-disposes of excess fuel from diet
-provides fuels in between meals
-interconverts fuels to glucose
and keto acids so brain has enough fuel

Front 239

brain

Back 239

requires supply of fuel and O2
cannot burn fatty acids
uses 20-25% REE

Front 240

muscle

Back 240

significant CHO reserves as glycogen
utilizes glucose or fat fuels
major reserve of body protein
spares brain fuels during exercuse

Front 241

RBC

Back 241

only glucose, lactate

Front 242

kidney

Back 242

uses ATP to excrete wastes excretes nonvolatile wastes
excretes excess acid

Front 243

lungs

Back 243

excretes volatile wastes (CO2)

Front 244

coupling energy requiring reactions with energy releasing reactions

Back 244

endergonic with exergonic

balance required globally in cell or organism

Front 245

synthetic operations coupled to energy production

Back 245

reflects sum of individual coupled reactions

Front 246

compare metabolic situations

Back 246

fed vs fasted vs starved

Front 247

type I diabetes

Back 247

no insulin

Front 248

type II diabetes

Back 248

insulin has little effect

Front 249

Alcoholism

Back 249

increases NADH

Front 250

insulin

Back 250

stimulates glucose to be transported into cell

activates phosphatase which activates pyruvate kinase
activates glycogen synthases
inactivates glycogen phosphorylase
inactivates glycogen phosphorylase kinase

Front 251

GLUT 4

Back 251

muscle and adipose

Front 252

GLUT 2

Back 252

High Km, low affinity
liver
induces glucokinase through insulin
have to have insulin around before liver will take it in

Front 253

Fructose 2,6 Bisphosphate

Back 253

made in response to insulin
activated by PFK1
activates glycolysis (not in any pathways)

Front 254

glycogen

Back 254

fasted state
break down liver glycogen send glucose into blood stream

activates protein kinase A
induces gluconeogenic enzymes
F2,6BP synthesis is inhibited (PFK2 is phosphorylated)
cAMP activated protein kinase
is stimulated to inhibit PK
activates gluconeogenic pathway and shuts off glycolysis
PKA phosphorylates GLYCOGEN SYNTHASE and GLYCOGEN PHOSPHORYLASE KINASE but only activates glycogen phosphorylase kinase to avoid a futile cycle

Front 255

TCA cycle

Back 255

regulated by high NADH and ATP levels (both turn off this cycle)
Insulin activates pyruvate dehydrogenase (PDH) phosphatase and thereby activates the PDH complex
PDH turns pyruvate into Acetyl CoA turning on the TCA cycle

Front 256

proteins

Back 256

insulin makes some AAs go into tissues easier

Front 257

FA synthesis

Back 257

glycolysis is going (with lots of insulin)
phosphatase activates Acetyl CoA Carboxylase
Insulin stimulates synthesis and secretion of lipoprotein lipase (LPL)
this breaks down triglycerides into FAs for storage (LPL activated by apoCII)
insulin induces FA synthesis enzymes
-citrate lyase
-AcCoA carboxylase
-FA synthase
insulin also induces NADPH synthesis, malic enzyme and G6PDH

Front 258

FA breakdown

Back 258

bring FAs into liver so they can be broken down to make KBs
PKA is important stimulating hormone sensitive lipase (HSL)
PKA inactivates Acetyl CoA carboxylase

Front 259

Liver

Back 259

donates NADH to ETC to make energy
HOMEOSTASIS
-carbohydrates
glycolysis/TCA
gluconeogenesis
storage of glycogen for glucose production
-AAs
liver uses all AAs but BCAA
urea cycle to remove extra ammonia
-Lipids
synthesis and secretion of bile acids and salts
beta oxidation
KB production
FA synthesis
VLDL packaging and secretion
HDL packaging and secretion
Uptake of chylo remnants
Uptake of HDL
SYNTHESIS/PROCESSING PRoteins
-Heme
synthesis in liver (and other tissues)
bilirubin concentration
-circulating proteins synthesis
albumin
haptoglobin, ceruloplasm
blood clotting factors
clotting inhibitors
acute phase proteins
-CYP450 system and oxidation reactions
ETOH oxidation
drug oxidation
-storage
vitamins
cholesterol
iron and other metals
-EXCRETION/FILTRATION
drugs after CYP450
bilirubin after conjugation
poisons from gut
DEFENSE
excretion of IgA (against bacteria in gut)
Macrophages (VonKupffer cells) and phagocytose bacteria

Front 260

Alcohol

Back 260

increases NADH concentration
-alcohol dehydrogenase and aldehyde dehydrogenase both generate NADH
ETOH+alcoholDH--> acetaldehyde + NADH --> acetate goes into muscle to be used to form Acetyl CoA for the TCA cycle
ACS(Acetyle CoA synthetase) to use acetate for energy
membrane fluidity is altered and can lead to toxic effects in brain
acetaldehyde forms products with other proteins
acetate gives high amounts of acetyl CoA which leads to increased FA synthesis (steatosis in alcoholics)
increases NADH/NAD ration will increase the amount of lactate going to pyruvate (inhibits gluconeogenesis and TCA cycle)
high NAD also inhibts FA B-oxidation
increases glycerophosphate (precursor to TG formation) leads to increase TG in liver

metabolism ETOH generates high NADH/NAD ratio
high NADH/NAD ratio inhibits FA B-oxidation and TCA cycle (FA accumulate)
FA reesterified to TG because high NADH/NAD ratio generates Glycerol-3-P from DHAP
High NADH/NAD ratio inhibits TCA cycle (oxaloacetate goes to malate)
High NADH/NAD ratio shifts OAA toward malate, acetyl CoA goes toward KB formation
cannot do gluconeogensis because pyruvate goes toward lactate because of high NADH/NAD ration (lactic acidemia)

Uric acid competes with other acids (lactic, salicylic, etc) for transport into kidney (break down DNA by acetaldehyde)

gluconeogenic precursor AAs (via pyruvate) not used for GNG because push towards lactate

alanine will go to pyruvate, pyruvate will go to lactate (causes hypoglycemia)
NADH are blocking PDH. so OAA is going toward malate which goes into cytosol and stops gluconeogenesis

Front 261

Type I db

Back 261

hormonal (no insulin, lots of glucagon)

Front 262

type II db

Back 262

hormonal, lots of insulin, does not work correctly, (no glucagon)

Front 263

glycolysis

Back 263

not much glucagon, lots of insulin
glucokinase is inducible (high Km)
PFK1 is active when low ATP, high AMP and high F2,6BP
PFK1 is inactive when high ATP, low AMP, high F 2,6BP
pyruvate kinase is active with insulin and inactive with glucagon

Front 264

gluconeogenesis

Back 264

low insulin, high glucagon levels
G-6-Phosphate is inducible with cortisol and cAMP via glucagon
Pyruvate carboxylase is activated by Acetyl CoA
PEP carboxykinase is inducible and activated by cAMP (via glucagon)

Front 265

FA oxidation

Back 265

fasted state, increase FA/TG from adipose (via HSL)
malonyl CoA inhibits newly synthesized FA transport into mitochondria via CPTI
mitochondria keeps compartments separated (all synthesis in cytosol)

Front 266

FA synthesis

Back 266

fed state, increase FA/TG from digestion, increase ATP, NADPH, Acetyl CoA, citrate (tca)

citrate activates Acetyl CoA carboxylase and is used to make Acetyl CoA

Cytosol - Malonyl CoA inhibits movement of acyl group into mitochondria

Front 267

TG breakdown

Back 267

no futile cycle because must make glycerol-3-phosphate from glucose and if there is no glucose there will be no TG synthesis

HSL breaksdown TG into FA to be used for energy. HSL controlled by glucagon (activate) insulin (inhibit)

TG breakdown by LPL to release FA from VLDL and chylomicrons
for storage in adipose or energy in muscle

Front 268

TG synthesis

Back 268

TG not synthesized from glycerol + FFA because no glycerol kinase in adipose tissue (most get from glucose)
TG only synthesized from glycerol derived from glucose
TG synthesis happens in liver

Front 269

glycogen breakdown

Back 269

glycogen phosphorylase is going to be active when you are breaking glycogen down because of the phosphate group that is on it
it will be inactive when dephosphorylated by a phosphatase
gylcogen phosphorylase will be active when there is low insulin and high glucagon because the body needs energy and breaks down glycogen

Front 270

glycogen synthesis

Back 270

glycogen synthase is active during synthesis
-dephosphorylated by phosphatase (to activate)
inactivated by PKA
glycogen synthase will be active when insulin is high and glucagon is low because the body has excess energy sources and can store it

Front 271

urea cycle on or off

Back 271

protein synthesis or proteolysis
feeds forward because there are a lot of AAs so the body wants to get rid of some of those nitrogens by putting them on Urea

Carbamoyl P synthetase
-CPSI allosterically inactivated by N-Acetyl glutatmate (NAG)
NAG not found in cycles only used to activate first step in urea cycle (NAG synthesized from glutamate and activated by arginine)
urea cycle enzymes are under induction or repression of synthesis
(high protein diet vs. prolonged fasting)

Front 272

biotin

Back 272

carboxylation reactions
pyruvate carboxylase (pyruvate-->OAA)
acetyl CoA carboxylase(acetyl coA-->malonyl)
propionylCoA carboxylase
post-translational carboxylases

Front 273

B1 Thiamine

Back 273

TPP
cofactor in oxidative decarboxylation of alpha-keto acids
-pyruvate dehydrogenase
-alpha-ketoglutarate dehydrogenase
-BCAA dehydrogenase

formation or degradation of alpha-ketols by transketolase

Front 274

B2 Riboflavin

Back 274

redox/oxidation reaction
used in TCA cycle and Beta-oxidation
biologically active as FMN and FAD

Front 275

B3 Niacin

Back 275

NAD/NADP are co-enzymes in redox reactions. accepts a hydride ion

Front 276

B5 pantothenic acid

Back 276

CoA
transfers acyl groups via a thiol group as activated thiol esters (CoA)

Front 277

B6 pyroxidine

Back 277

PLP
decarboxylation
transamination
synthesis (heme): glycine (AA) is decarboxylated
AA decarboxylation to form neurotransmitters (GABA, 5HT, histamine)
transamination reactions
a step in tryptophan degradation

Front 278

B12 cobalamin

Back 278

nucleotide synthesis
transfers methyl group to form methionine
involved in pyrimidine nucleotide synthesis
methylmalonyl coA-->succinyl CoA (methylmalonyl coA mutase)
carbons from val, ile, thr, thymine, last 3C of odd chain FA-->succinyl CoA
odd chain FA metabolism and BCAA metabolism

Front 279

folic acid

Back 279

receives 1C fragments from donors(ser, gly, his, etc( and transfers to intermediates in synthesis of AA, purines, thymidine
one carbon metabolism

Front 280

C(ascorbic acid)

Back 280

antioxidant, free radical scavenger in aqueous environment
hydroxylation of prolyl residues on collagen by prolyl hydroxylase in preparation for cross-linking

Front 281

d (sterols)

Back 281

hormone like functions to maintain CA2+ levels
increases uptake Ca++ by intestine
minimizes loss Ca++ by kidney
stimulates bone resorption if necessary

Front 282

E (alpha-tocopherol)

Back 282

antioxidant
lipophilic free radical scavenger
protects against lipid peroxidation

Front 283

K

Back 283

modify clotting factors II, VII, IX, X
carboxylation of glutamate to gamma-carboxy-glutamate

Front 284

inborn errors of metabolism

Back 284

rare genetic diseases
blockage in metabolic pathway
lower activity/complete deficiency of specific enzyme
substrate will accumulate, product will be low
substrate will then take other pathways
accumulate in tissues and organs and become toxic and harmful

pattern of inheritance
-can be young/infant onset or adult
higher severity with younger onset (dtect disease with pheotypic expression)
milder with adult onset

Front 285

AA diseases (PKU) organic acids, galactosemia, urea cycle disease

Back 285

most common IBM
1/4200
PKU is most common

Front 286

inborn errors of metabolism

Back 286

rare genetic diseases
blockage in metabolic pathway
lower activity/complete deficiency of specific enzyme
substrate will accumulate, product will be low
substrate will then take other pathways
accumulate in tissues and organs and become toxic and harmful

pattern of inheritance
-can be young/infant onset or adult
higher severity with younger onset (dtect disease with pheotypic expression)
milder with adult onset

Front 287

inborn errors of metabolism

Back 287

rare genetic diseases
blockage in metabolic pathway
lower activity/complete deficiency of specific enzyme
substrate will accumulate, product will be low
substrate will then take other pathways
accumulate in tissues and organs and become toxic and harmful

pattern of inheritance
-can be young/infant onset or adult
higher severity with younger onset (dtect disease with pheotypic expression)
milder with adult onset

Front 288

Lysosomal storage disease

Back 288

1/12000

Front 289

AA diseases (PKU) organic acids, galactosemia, urea cycle disease

Back 289

most common IBM
1/4200
PKU is most common

Front 290

Lysosomal storage disease

Back 290

1/12000

Front 291

Peroxisomal disorder

Back 291

1/30000

Front 292

AA diseases (PKU) organic acids, galactosemia, urea cycle disease

Back 292

most common IBM
1/4200
PKU is most common

Front 293

Peroxisomal disorder

Back 293

1/30000

Front 294

Lysosomal storage disease

Back 294

1/12000

Front 295

respiratory chain-based mitochondrial disease

Back 295

1/33000

Front 296

respiratory chain-based mitochondrial disease

Back 296

1/33000

Front 297

Peroxisomal disorder

Back 297

1/30000

Front 298

glycogen storage disease

Back 298

1/43000

Front 299

respiratory chain-based mitochondrial disease

Back 299

1/33000

Front 300

glycogen storage disease

Back 300

1/43000

Front 301

inborn errors of metabolism

Back 301

rare genetic diseases
blockage in metabolic pathway
lower activity/complete deficiency of specific enzyme
substrate will accumulate, product will be low
substrate will then take other pathways
accumulate in tissues and organs and become toxic and harmful

pattern of inheritance
-can be young/infant onset or adult
higher severity with younger onset (dtect disease with pheotypic expression)
milder with adult onset

Front 302

lysosomes

Back 302

cellular organelles that recycle macromolecules (proteins, glycoproteins, lipids, phospholipids, sphingolipids)
break down for reuse
~70 enzymes in lysosomes
optimal activity at pH=5

Front 303

glycogen storage disease

Back 303

1/43000

Front 304

lysosomes

Back 304

cellular organelles that recycle macromolecules (proteins, glycoproteins, lipids, phospholipids, sphingolipids)
break down for reuse
~70 enzymes in lysosomes
optimal activity at pH=5

Front 305

lysosomal storage disorders
characteristics

Back 305

defect can be at particular reaction site of lysosomal enzyme or coenzyme of reaction or posttranslational modification protein or lysosomal transport protein

results in accumulation of substrate in lysosome
more than 5 different LSDs
most autosomal recessive (Hunter and Fabry's are X linked)

onset typically in infancy or early childhood

phenotype-genotype heterogeneity exists
in newborns, phenotypes are fatal and often go unrecognized
(many symptoms, can be misdiagnosed)
milder symptoms may be undiagnosed for years

CNS involvement (neuro disorders, mental disorders)
organomegaly (spleen, liver)
connective tissue
ocular pathology (something wrong with eye nerves)

Front 306

AA diseases (PKU) organic acids, galactosemia, urea cycle disease

Back 306

most common IBM
1/4200
PKU is most common

Front 307

lysosomes

Back 307

cellular organelles that recycle macromolecules (proteins, glycoproteins, lipids, phospholipids, sphingolipids)
break down for reuse
~70 enzymes in lysosomes
optimal activity at pH=5

Front 308

inborn errors of metabolism

Back 308

rare genetic diseases
blockage in metabolic pathway
lower activity/complete deficiency of specific enzyme
substrate will accumulate, product will be low
substrate will then take other pathways
accumulate in tissues and organs and become toxic and harmful

pattern of inheritance
-can be young/infant onset or adult
higher severity with younger onset (dtect disease with pheotypic expression)
milder with adult onset

Front 309

lysosomal storage disorders
characteristics

Back 309

defect can be at particular reaction site of lysosomal enzyme or coenzyme of reaction or posttranslational modification protein or lysosomal transport protein

results in accumulation of substrate in lysosome
more than 5 different LSDs
most autosomal recessive (Hunter and Fabry's are X linked)

onset typically in infancy or early childhood

phenotype-genotype heterogeneity exists
in newborns, phenotypes are fatal and often go unrecognized
(many symptoms, can be misdiagnosed)
milder symptoms may be undiagnosed for years

CNS involvement (neuro disorders, mental disorders)
organomegaly (spleen, liver)
connective tissue
ocular pathology (something wrong with eye nerves)

Front 310

LSD causes

Back 310

primary (genetic) or secondary (changes cellular processes, secondary biochemical pathways)

Front 311

Lysosomal storage disease

Back 311

1/12000

Front 312

lysosomal storage disorders
characteristics

Back 312

defect can be at particular reaction site of lysosomal enzyme or coenzyme of reaction or posttranslational modification protein or lysosomal transport protein

results in accumulation of substrate in lysosome
more than 5 different LSDs
most autosomal recessive (Hunter and Fabry's are X linked)

onset typically in infancy or early childhood

phenotype-genotype heterogeneity exists
in newborns, phenotypes are fatal and often go unrecognized
(many symptoms, can be misdiagnosed)
milder symptoms may be undiagnosed for years

CNS involvement (neuro disorders, mental disorders)
organomegaly (spleen, liver)
connective tissue
ocular pathology (something wrong with eye nerves)

Front 313

LSD causes

Back 313

primary (genetic) or secondary (changes cellular processes, secondary biochemical pathways)

Front 314

AA diseases (PKU) organic acids, galactosemia, urea cycle disease

Back 314

most common IBM
1/4200
PKU is most common

Front 315

glycogen storage disease 2
(Pompe)

Back 315

LSD

Front 316

glycogen storage disease 2
(Pompe)

Back 316

LSD

Front 317

LSD causes

Back 317

primary (genetic) or secondary (changes cellular processes, secondary biochemical pathways)

Front 318

Peroxisomal disorder

Back 318

1/30000

Front 319

Lysosomal storage disease

Back 319

1/12000

Front 320

glycogen storage disease 2
(Pompe)

Back 320

LSD

Front 321

respiratory chain-based mitochondrial disease

Back 321

1/33000

Front 322

Peroxisomal disorder

Back 322

1/30000

Front 323

glycogen storage disease

Back 323

1/43000

Front 324

respiratory chain-based mitochondrial disease

Back 324

1/33000

Front 325

lysosomes

Back 325

cellular organelles that recycle macromolecules (proteins, glycoproteins, lipids, phospholipids, sphingolipids)
break down for reuse
~70 enzymes in lysosomes
optimal activity at pH=5

Front 326

inborn errors of metabolism

Back 326

rare genetic diseases
blockage in metabolic pathway
lower activity/complete deficiency of specific enzyme
substrate will accumulate, product will be low
substrate will then take other pathways
accumulate in tissues and organs and become toxic and harmful

pattern of inheritance
-can be young/infant onset or adult
higher severity with younger onset (dtect disease with pheotypic expression)
milder with adult onset

Front 327

inborn errors of metabolism

Back 327

rare genetic diseases
blockage in metabolic pathway
lower activity/complete deficiency of specific enzyme
substrate will accumulate, product will be low
substrate will then take other pathways
accumulate in tissues and organs and become toxic and harmful

pattern of inheritance
-can be young/infant onset or adult
higher severity with younger onset (dtect disease with pheotypic expression)
milder with adult onset

Front 328

inborn errors of metabolism

Back 328

rare genetic diseases
blockage in metabolic pathway
lower activity/complete deficiency of specific enzyme
substrate will accumulate, product will be low
substrate will then take other pathways
accumulate in tissues and organs and become toxic and harmful

pattern of inheritance
-can be young/infant onset or adult
higher severity with younger onset (dtect disease with pheotypic expression)
milder with adult onset

Front 329

inborn errors of metabolism

Back 329

rare genetic diseases
blockage in metabolic pathway
lower activity/complete deficiency of specific enzyme
substrate will accumulate, product will be low
substrate will then take other pathways
accumulate in tissues and organs and become toxic and harmful

pattern of inheritance
-can be young/infant onset or adult
higher severity with younger onset (dtect disease with pheotypic expression)
milder with adult onset

Front 330

inborn errors of metabolism

Back 330

rare genetic diseases
blockage in metabolic pathway
lower activity/complete deficiency of specific enzyme
substrate will accumulate, product will be low
substrate will then take other pathways
accumulate in tissues and organs and become toxic and harmful

pattern of inheritance
-can be young/infant onset or adult
higher severity with younger onset (dtect disease with pheotypic expression)
milder with adult onset

Front 331

inborn errors of metabolism

Back 331

rare genetic diseases
blockage in metabolic pathway
lower activity/complete deficiency of specific enzyme
substrate will accumulate, product will be low
substrate will then take other pathways
accumulate in tissues and organs and become toxic and harmful

pattern of inheritance
-can be young/infant onset or adult
higher severity with younger onset (dtect disease with pheotypic expression)
milder with adult onset

Front 332

lysosomal storage disorders
characteristics

Back 332

defect can be at particular reaction site of lysosomal enzyme or coenzyme of reaction or posttranslational modification protein or lysosomal transport protein

results in accumulation of substrate in lysosome
more than 5 different LSDs
most autosomal recessive (Hunter and Fabry's are X linked)

onset typically in infancy or early childhood

phenotype-genotype heterogeneity exists
in newborns, phenotypes are fatal and often go unrecognized
(many symptoms, can be misdiagnosed)
milder symptoms may be undiagnosed for years

CNS involvement (neuro disorders, mental disorders)
organomegaly (spleen, liver)
connective tissue
ocular pathology (something wrong with eye nerves)

Front 333

glycogen storage disease

Back 333

1/43000

Front 334

AA diseases (PKU) organic acids, galactosemia, urea cycle disease

Back 334

most common IBM
1/4200
PKU is most common

Front 335

AA diseases (PKU) organic acids, galactosemia, urea cycle disease

Back 335

most common IBM
1/4200
PKU is most common

Front 336

LSD causes

Back 336

primary (genetic) or secondary (changes cellular processes, secondary biochemical pathways)

Front 337

AA diseases (PKU) organic acids, galactosemia, urea cycle disease

Back 337

most common IBM
1/4200
PKU is most common

Front 338

lysosomes

Back 338

cellular organelles that recycle macromolecules (proteins, glycoproteins, lipids, phospholipids, sphingolipids)
break down for reuse
~70 enzymes in lysosomes
optimal activity at pH=5

Front 339

AA diseases (PKU) organic acids, galactosemia, urea cycle disease

Back 339

most common IBM
1/4200
PKU is most common

Front 340

AA diseases (PKU) organic acids, galactosemia, urea cycle disease

Back 340

most common IBM
1/4200
PKU is most common

Front 341

Lysosomal storage disease

Back 341

1/12000

Front 342

Lysosomal storage disease

Back 342

1/12000

Front 343

AA diseases (PKU) organic acids, galactosemia, urea cycle disease

Back 343

most common IBM
1/4200
PKU is most common

Front 344

glycogen storage disease 2
(Pompe)

Back 344

LSD

Front 345

Lysosomal storage disease

Back 345

1/12000

Front 346

Lysosomal storage disease

Back 346

1/12000

Front 347

Peroxisomal disorder

Back 347

1/30000

Front 348

Lysosomal storage disease

Back 348

1/12000

Front 349

lysosomal storage disorders
characteristics

Back 349

defect can be at particular reaction site of lysosomal enzyme or coenzyme of reaction or posttranslational modification protein or lysosomal transport protein

results in accumulation of substrate in lysosome
more than 5 different LSDs
most autosomal recessive (Hunter and Fabry's are X linked)

onset typically in infancy or early childhood

phenotype-genotype heterogeneity exists
in newborns, phenotypes are fatal and often go unrecognized
(many symptoms, can be misdiagnosed)
milder symptoms may be undiagnosed for years

CNS involvement (neuro disorders, mental disorders)
organomegaly (spleen, liver)
connective tissue
ocular pathology (something wrong with eye nerves)

Front 350

Peroxisomal disorder

Back 350

1/30000

Front 351

Lysosomal storage disease

Back 351

1/12000

Front 352

Peroxisomal disorder

Back 352

1/30000

Front 353

Peroxisomal disorder

Back 353

1/30000

Front 354

LSD causes

Back 354

primary (genetic) or secondary (changes cellular processes, secondary biochemical pathways)

Front 355

respiratory chain-based mitochondrial disease

Back 355

1/33000

Front 356

Peroxisomal disorder

Back 356

1/30000

Front 357

Peroxisomal disorder

Back 357

1/30000

Front 358

respiratory chain-based mitochondrial disease

Back 358

1/33000

Front 359

respiratory chain-based mitochondrial disease

Back 359

1/33000

Front 360

respiratory chain-based mitochondrial disease

Back 360

1/33000

Front 361

glycogen storage disease 2
(Pompe)

Back 361

LSD

Front 362

respiratory chain-based mitochondrial disease

Back 362

1/33000

Front 363

glycogen storage disease

Back 363

1/43000

Front 364

respiratory chain-based mitochondrial disease

Back 364

1/33000

Front 365

glycogen storage disease

Back 365

1/43000

Front 366

glycogen storage disease

Back 366

1/43000

Front 367

glycogen storage disease

Back 367

1/43000

Front 368

glycogen storage disease

Back 368

1/43000

Front 369

lysosomes

Back 369

cellular organelles that recycle macromolecules (proteins, glycoproteins, lipids, phospholipids, sphingolipids)
break down for reuse
~70 enzymes in lysosomes
optimal activity at pH=5

Front 370

lysosomes

Back 370

cellular organelles that recycle macromolecules (proteins, glycoproteins, lipids, phospholipids, sphingolipids)
break down for reuse
~70 enzymes in lysosomes
optimal activity at pH=5

Front 371

lysosomes

Back 371

cellular organelles that recycle macromolecules (proteins, glycoproteins, lipids, phospholipids, sphingolipids)
break down for reuse
~70 enzymes in lysosomes
optimal activity at pH=5

Front 372

lysosomes

Back 372

cellular organelles that recycle macromolecules (proteins, glycoproteins, lipids, phospholipids, sphingolipids)
break down for reuse
~70 enzymes in lysosomes
optimal activity at pH=5

Front 373

glycogen storage disease

Back 373

1/43000

Front 374

lysosomes

Back 374

cellular organelles that recycle macromolecules (proteins, glycoproteins, lipids, phospholipids, sphingolipids)
break down for reuse
~70 enzymes in lysosomes
optimal activity at pH=5

Front 375

lysosomal storage disorders
characteristics

Back 375

defect can be at particular reaction site of lysosomal enzyme or coenzyme of reaction or posttranslational modification protein or lysosomal transport protein

results in accumulation of substrate in lysosome
more than 5 different LSDs
most autosomal recessive (Hunter and Fabry's are X linked)

onset typically in infancy or early childhood

phenotype-genotype heterogeneity exists
in newborns, phenotypes are fatal and often go unrecognized
(many symptoms, can be misdiagnosed)
milder symptoms may be undiagnosed for years

CNS involvement (neuro disorders, mental disorders)
organomegaly (spleen, liver)
connective tissue
ocular pathology (something wrong with eye nerves)

Front 376

lysosomes

Back 376

cellular organelles that recycle macromolecules (proteins, glycoproteins, lipids, phospholipids, sphingolipids)
break down for reuse
~70 enzymes in lysosomes
optimal activity at pH=5

Front 377

lysosomal storage disorders
characteristics

Back 377

defect can be at particular reaction site of lysosomal enzyme or coenzyme of reaction or posttranslational modification protein or lysosomal transport protein

results in accumulation of substrate in lysosome
more than 5 different LSDs
most autosomal recessive (Hunter and Fabry's are X linked)

onset typically in infancy or early childhood

phenotype-genotype heterogeneity exists
in newborns, phenotypes are fatal and often go unrecognized
(many symptoms, can be misdiagnosed)
milder symptoms may be undiagnosed for years

CNS involvement (neuro disorders, mental disorders)
organomegaly (spleen, liver)
connective tissue
ocular pathology (something wrong with eye nerves)

Front 378

lysosomal storage disorders
characteristics

Back 378

defect can be at particular reaction site of lysosomal enzyme or coenzyme of reaction or posttranslational modification protein or lysosomal transport protein

results in accumulation of substrate in lysosome
more than 5 different LSDs
most autosomal recessive (Hunter and Fabry's are X linked)

onset typically in infancy or early childhood

phenotype-genotype heterogeneity exists
in newborns, phenotypes are fatal and often go unrecognized
(many symptoms, can be misdiagnosed)
milder symptoms may be undiagnosed for years

CNS involvement (neuro disorders, mental disorders)
organomegaly (spleen, liver)
connective tissue
ocular pathology (something wrong with eye nerves)

Front 379

lysosomal storage disorders
characteristics

Back 379

defect can be at particular reaction site of lysosomal enzyme or coenzyme of reaction or posttranslational modification protein or lysosomal transport protein

results in accumulation of substrate in lysosome
more than 5 different LSDs
most autosomal recessive (Hunter and Fabry's are X linked)

onset typically in infancy or early childhood

phenotype-genotype heterogeneity exists
in newborns, phenotypes are fatal and often go unrecognized
(many symptoms, can be misdiagnosed)
milder symptoms may be undiagnosed for years

CNS involvement (neuro disorders, mental disorders)
organomegaly (spleen, liver)
connective tissue
ocular pathology (something wrong with eye nerves)

Front 380

lysosomal storage disorders
characteristics

Back 380

defect can be at particular reaction site of lysosomal enzyme or coenzyme of reaction or posttranslational modification protein or lysosomal transport protein

results in accumulation of substrate in lysosome
more than 5 different LSDs
most autosomal recessive (Hunter and Fabry's are X linked)

onset typically in infancy or early childhood

phenotype-genotype heterogeneity exists
in newborns, phenotypes are fatal and often go unrecognized
(many symptoms, can be misdiagnosed)
milder symptoms may be undiagnosed for years

CNS involvement (neuro disorders, mental disorders)
organomegaly (spleen, liver)
connective tissue
ocular pathology (something wrong with eye nerves)

Front 381

LSD causes

Back 381

primary (genetic) or secondary (changes cellular processes, secondary biochemical pathways)

Front 382

LSD causes

Back 382

primary (genetic) or secondary (changes cellular processes, secondary biochemical pathways)

Front 383

LSD causes

Back 383

primary (genetic) or secondary (changes cellular processes, secondary biochemical pathways)

Front 384

LSD causes

Back 384

primary (genetic) or secondary (changes cellular processes, secondary biochemical pathways)

Front 385

LSD causes

Back 385

primary (genetic) or secondary (changes cellular processes, secondary biochemical pathways)

Front 386

lysosomal storage disorders
characteristics

Back 386

defect can be at particular reaction site of lysosomal enzyme or coenzyme of reaction or posttranslational modification protein or lysosomal transport protein

results in accumulation of substrate in lysosome
more than 5 different LSDs
most autosomal recessive (Hunter and Fabry's are X linked)

onset typically in infancy or early childhood

phenotype-genotype heterogeneity exists
in newborns, phenotypes are fatal and often go unrecognized
(many symptoms, can be misdiagnosed)
milder symptoms may be undiagnosed for years

CNS involvement (neuro disorders, mental disorders)
organomegaly (spleen, liver)
connective tissue
ocular pathology (something wrong with eye nerves)

Front 387

glycogen storage disease 2
(Pompe)

Back 387

LSD

Front 388

glycogen storage disease 2
(Pompe)

Back 388

LSD

Front 389

glycogen storage disease 2
(Pompe)

Back 389

LSD

Front 390

glycogen storage disease 2
(Pompe)

Back 390

LSD

Front 391

glycogen storage disease 2
(Pompe)

Back 391

LSD

Front 392

LSD causes

Back 392

primary (genetic) or secondary (changes cellular processes, secondary biochemical pathways)

Front 393

glycogen storage disease 2
(Pompe)

Back 393

LSD

Front 394

sphingolipidoses

Back 394

Fabry, Farber, Gaucher, Tay-Sachs, Niemann-Pick, GM2 Gangliosidosis Sandhoff, Krabbe, MLD

Front 395

Mucopolysaccharidoses

Back 395

MPSI or Hurler, MPSII or Hunter, MPSIII or Sanfilippo, MPSIV or MOrquio, MPSVI or Maroteaux-Lamy, MPSVII or SLy

Front 396

other LSDs

Back 396

glycoproteinoses, neuronal ceroid liposuscinoses, transport defects

Front 397

mucolipidoses

Back 397

MLII, MLIII

Front 398

treatment of LSDs

Back 398

based on the disease pathway, enzyme to substrate (low vs high) defective lysosomal enzyme is a hydrolase
-protein re-engineering
-bone marrow and stem cell transplantation
-gene therapy
-enzyme replacement therapy (ERT)
enzyme enhancement therapy (chaperones)
substrate reduction therapy
identify secondary biochemical pathways affected by substrate accumulation and try to intervene.

Front 399

Pompe (GSD II)

Back 399

due to a missing lysosomal debranching enzyme in lysosome, alpha-glucosidase
results in accumulation of glycogen (cant break down to glucose)
because in lysosome, disease doesnt contribute to hypoglycemia
contributes to skeletal and cardiac muscles and liver
lysosomes normally small, become distended

three forms
-infantile
death by two years
progressive muscle weakness
profound hypotonia
macroglossia (enlarged tongue)
cardiomegaly and cardiac failure
-Late Juve/Adult form
milder than infantile, greater variation in symptom onset age
some glucosidase activty (some debranching enzyme present)
progressive proximal weakness in trunk
exercise intolerance
hypotonia
hepatomegaly
absence of severe cardiac involvement (some slight)
respiratory insufficiency
death usually respiratory failure

Front 400

sphingolipidoses

Back 400

LSD where enzyme affected is generally lysosomal hydrolase (degrades sphingolipids)
deficiency of enzyme itself or lack of an enzyme transporter in lysosomal membrane
accumulation of sphingolipids
hallmark symptom is progressive neurodegeneration
autosomal recessive disorder (Fabry's is X linked)
MR is common to many of these diseases

sphingolipids
glycosphingolipid is a type of sphingolipid
-sphingosine backbone with either a glucose or galactose attached

four major classes
-cerebrosides (single glucose/galactose moeity)
glucocerebroside/galactocerebroside
-Globosides
similar to cerebroside, but has 2+ sugar molecules
-Gangliosides
similar to globosides, but has a sialic acid
-Sulfatides
have sulfuric acid attached by an ester to galactocerebroside

sphingosine+FA--> ceramide
phosphate+alcohol--> sphingomyelin

glycosphingolipid must have glucose or galactose
globosides have more than one sugar
galgliosides have sialic acid

ceramide sphingolipids plus FA create ceramide
(add more sugar, get cerebrosides (gluco/galactocerebrosides)

degraded by enzymes
-galactocylceramidase (krabbe disorder if missing)
-glucocylceramidase (gaucher disorder if missing)

Hexosaminidase A or B def. is Tay-Sachs or Sandoff's
Alpha-galactosidase A def. results in Fabry's

Front 401

Tay Sachs

Back 401

def. Hexasoaminidase A which catalyzes degradation of gangliosides GM2
gangliosides are synthesized and degraded very rapidly (important in early life and brain development)
accumulation of gangliosides in tissues is harmful and can be fatal
development is normal for first few months, then symptoms appear
-nerve cells become distended with fatty materials
-affects mental function and physical abilties
-Lose all muscle tone

carriers of disease are missing enzyme
presently no treatment (anticonvulsants for seizure control)
Ashkenazi Jews mostly Affects
symptoms (cherry red spots in eyes, blindness, deafness, inability to swallow due to muscle atrophy and paralysis
dementia, seizures,
late age of onset can be 20-30 years (very rare)
normal sounds abruptly startle child
1/27 jews are carriers, 1/3000 jewish babies born with disease

Front 402

Fabry's

Back 402

deficiency of alpha-galactosidase enzyme
mutation causes buildup of globosides or ceramide trihexoside (accumulates in eyes, kidneys, nervous tissue, CV system)
X linked lipid storage disease
enzyme replacement therapy approved by FDA is used for Tx
patients die prematurely from strokes, heart disease, renal failure

symptoms
-burning sensation when sweat or exercise
corneal cloudiness in eye
angiokeratomas (raised reddish blemishes on skin of chest and back)
renal failure

Front 403

Metachromatic Leukodystrophy

Back 403

MLD
lack of aryl sulfutase A, results in buildup of sulfatides
lipid is important for protection on myelin sheath and what surrounds nerve tissue
kidneys,gallbladder, other organs affects
autosomal recessive
three forms

late infantile
begins 1-2 years old
juvenile
begins 4-12 years old
adult/late stage juvenile
after 14 years

symptoms
issues with muscle tone and movement
walking, ,muscle control, falls, feeding, swallowing difficulties
decreased mental function
behavior issues
nerve functions in general
metachromatic granules

Front 404

gaucher disease

Back 404

defect in beta-glucosidase
accumulation of glucocerebroside
-accumulates in macrophages, histologically called Gaucher cells
can causes splenomegaly and hepatomegaly, issues with bone marrow and anemia

three types

type I
most common in general and ashkenazi jewish
bone disease, anemia, splenomegaly

type II disease
infancy, neurological involvement, rapidly lead to early death

type III
spleen, liver, brain problems
patient has longer life


MR
loss of bone density, fractures, bone pain
seizures

Front 405

gaucher disease

Back 405

defect in beta-glucosidase
accumulation of glucocerebroside
-accumulates in macrophages, histologically called Gaucher cells
can causes splenomegaly and hepatomegaly, issues with bone marrow and anemia

three types

type I
most common in general and ashkenazi jewish
bone disease, anemia, splenomegaly

type II disease
infancy, neurological involvement, rapidly lead to early death

type III
spleen, liver, brain problems
patient has longer life


MR
loss of bone density, fractures, bone pain
seizures

Front 406

Neimann Pick disease

Back 406

accumulation of sphingomyelin in liver, spleen, lung, bone marrow, brain

multi organ involvement causes many different symptoms
enlargement of organs
classic type A variant is a missense mutation that leads to complete deficiency of the sphingomyelinase enzyme

affected cells become enlarged
histologically lipid laden macrophages (sea-blue histiocytes)
age of onset is different

Type I
Type A (first few months after birth)
abdominal area gets larger
cherry red spots in eye
loss of motor skills early in life
type B
milder, occurs later in childhood, adolescence
abdominal swelling, splenomegaly
no brain or nervous system involvement
no loss of motor skills

Type II
type C (handout)
Type D
similar to type c

Front 407

Neimann Pick disease

Back 407

accumulation of sphingomyelin in liver, spleen, lung, bone marrow, brain

multi organ involvement causes many different symptoms
enlargement of organs
classic type A variant is a missense mutation that leads to complete deficiency of the sphingomyelinase enzyme

affected cells become enlarged
histologically lipid laden macrophages (sea-blue histiocytes)
age of onset is different

Type I
Type A (first few months after birth)
abdominal area gets larger
cherry red spots in eye
loss of motor skills early in life
type B
milder, occurs later in childhood, adolescence
abdominal swelling, splenomegaly
no brain or nervous system involvement
no loss of motor skills

Type II
type C (handout)
Type D
similar to type c

Front 408

Sandhoff disease, GM1 gangliosidosis, Krabbe

Back 408

handout

Front 409

Sandhoff disease, GM1 gangliosidosis, Krabbe

Back 409

handout

Front 410

Mucopolysaccharidoses MPS

Back 410

MPS I Hurler and Scheie syndromes

hurler-most severe
developmental delays, severe respiratory, do not live beyond ten

scheie: less severe
normal intelligence, less progressive physical problems, normal looking features
can live to decades of age

MPS II Hunter Disease

MPS III-IX

normal degradation of carbohydrate chains of glycosaminoglycans
defective enzyme that is important in the glycosaminoglycan pathway
can be normal intellect to profound MR

symptoms
rough facial features (gargoyle-like), thick lips, enlarged mouth and tongue
dwarfism, abnormal bone size/shape
thickened skin
hepato/splenomegaly

mucopolysaccharides (glycosaminoglycans) are involved in MPS

glucosamine glycans derived from glucose

heparin and dermatan sulfate are derived from glucose
-component of joints, synovial fluid, lubricants, collagen binders, anticoagulant (heparin)

hyaluronic acid
-improves viscosity and elasticity of synovial fluid
tx for osteoarthrities
corrects facial wrinkles/folds

MPS I: Hurler
def. alpha-L-iduronidase
accumulation of dermatan and heparin sulfate
causes tissue and organ dysfunction


broad mouth, square jaw, receding chin
corneal clouding
dwarfism bc joint deformities


MPS II HUnter's syndrome
def. enzyme iduronate sulfatase
still accumulate dermatan/heparin sulfate
Xlinked
no corneal clouding

Front 411

Mucopolysaccharidoses MPS

Back 411

MPS I Hurler and Scheie syndromes

hurler-most severe
developmental delays, severe respiratory, do not live beyond ten

scheie: less severe
normal intelligence, less progressive physical problems, normal looking features
can live to decades of age

MPS II Hunter Disease

MPS III-IX

normal degradation of carbohydrate chains of glycosaminoglycans
defective enzyme that is important in the glycosaminoglycan pathway
can be normal intellect to profound MR

symptoms
rough facial features (gargoyle-like), thick lips, enlarged mouth and tongue
dwarfism, abnormal bone size/shape
thickened skin
hepato/splenomegaly

mucopolysaccharides (glycosaminoglycans) are involved in MPS

glucosamine glycans derived from glucose

heparin and dermatan sulfate are derived from glucose
-component of joints, synovial fluid, lubricants, collagen binders, anticoagulant (heparin)

hyaluronic acid
-improves viscosity and elasticity of synovial fluid
tx for osteoarthrities
corrects facial wrinkles/folds

MPS I: Hurler
def. alpha-L-iduronidase
accumulation of dermatan and heparin sulfate
causes tissue and organ dysfunction


broad mouth, square jaw, receding chin
corneal clouding
dwarfism bc joint deformities


MPS II HUnter's syndrome
def. enzyme iduronate sulfatase
still accumulate dermatan/heparin sulfate
Xlinked
no corneal clouding

Front 412

Mucolipidoses

Back 412

handout

Front 413

Mucolipidoses

Back 413

handout

Front 414

ways to measure metals

Back 414

chemical
-chemical chelator (will bind and change color, spectrophotometric assay)
flame inductive analysis
-burn, observe light refractions (more accurate, more sensitive)
ICP-MS (inductively coupled plasma mass spectrometry)
burn then run through mass spec
picks up many contaminants
difficult to discern between mineral and contaminant

Front 415

Mg and Ca

Back 415

soft alkaline metals
diffuse in and out because not tightly bound to enzymes
concentration is important

Front 416

transition metals

Back 416

tend to be held more tightly to proteins
bound for functionality (co-factors) but also safety, dont want them freely floating around body
some are not necessary but may be helpful (fluoride stabilize tooth enamel)

Front 417

water and salts

Back 417

intra/extracellular ion concentration can differe by 2 orders of magnitude
gradient drives cellular reactions (i.e. symporter diffusion H+ pulls in lactose)
(i.e. symporter pulls glucose into cell on one side, falls down gradient in other)

cell membranes permeable to H2) (aquaporins and ion channels allow this) need to maintain solute/water concentration to prevent lysis or cell shrinking
extracellular fluids act as conduit around cells, using entire surface area for exchange

volume estimate for 73kg person
24L intracellular
16L liquid extracelular
-interstitial volume 11.2L
plasma volume 3.2 L
Transcellular (inside organs) 1.6L

TBW estimate (Liters) = BW(lbs)/4 subtract 10% for obese person, add 10% for lean person
women have 10% less water than man of similar bodyweight

osmolality is particle(colute) concentration of fluid, units millosmoles/kg (mos-mol/kg)

Eextracellular fluid osmolality=intracellular fluid (to prevent lysis/shrinking)
ECF solutes (or osmoles) are very different from ICF due to action of transporters and active pumps and diff. permeability of membrances
ECF solutes are Na, Cl, HCO3
ICF solutes are K and organic phosphate esters (ATP, creatine phosphate, phospholipids, UTP, GTP,)
contributes to electrical charge

some soutes restricted to either ecf or icf and determine the effective osmolality of that compartment

since Na is mostly ECF, total body content reflects the ECF, same for K and ICF

cells can alter these levels in extreme situations

proteins estimated to be 15mEq, but difficult to measure due to size differences
serum albumin responsible for ~80% osmotic pressure of blood

milliequivalents=millimolar (when only one ionizable group)
mEq=2XmMolar
if there are two charges
mmol stays the same, must adjust for equivalents
if there are multiple ionizable groups with different pKs it is more pH dependent

proteins average to about 15mEw because they have many ionizable charges dependent on pH and salt concentrations

Front 418

water and sodium

Back 418

Na and K are main macrominerals

normal osmolality of plasma is 275-290 mosmol/kg and maintained by mechanisms that can detect 1-2% changes

avg western diet exceeds 150mmoles NACL per day (more than required)

avg 70kg man contains 100g sodium, half in bone, 40% ecf
recommended intake 2400, usual intake 3000-6000mg/day
requirement 500mg/day

can lead to hypertension, is a genetic component to na sensitivity and concentrations will affect people differently

Front 419

water and sodium loss

Back 419

water is lost from skin by sweating, liquid gets on surface, evaporates away, increases entropy of system, takes away energy, cools you off
mainly depends on heat and caloric expenditure
water is lost by exhaling, but also same amount created by metabolism (end product of cytochrome oxidase in ETC)
net activity of GI tract down to jejunum is secretion of water and electrolytes
net activty from jejunum to colon is reabsorption of water
typically ~100mL water per day excreted with feces
ingested food/water becomes isotonic so if vomit or have diarrhea lose ions
(cholera, lose water and ions, die quickly)

diarrheal fluid is close to isotonic, can lose liters

water/salt loss in urine is variable

Front 420

water and potassium

Back 420

recommended intake 3500mg
usual 4000-5000/day
requirement 2000mg
too much K will disrupt normal cellular function and cause death

na/k ratio linked to hypertension

deficiency of K heart arrythmias, muscle weakness, increased blood pH (alkalosis)

excess K cardiac arrest,

Front 421

Calcium

Back 421

regulate intracellular enzyme activities
secretory processes (nerve conductance, pancreatic enzymes, milk protein release)
blood clotting (K assists in binding gamma-carboxy-gluatamate to Ca)
muscle contraction
structure/growth of bones and teeth
binds to proteins affecting function
intracellular Ca can be .1uM (10,000x lower than ECF)
large variation in magnitude allows for dynamic range in cellular signaling
second messenger function
hormone-receptor interactions
-i.e. epi released from adrenal medulla, binds alpha receptors in liver, activates glycogenolysis and inhibits glycogen synthesis mainly by raising Ca levels in liver

calmodulin binding regulates many proteins and processes such as muscle contraction and inflammation, is a key regulator of many Ca dependent proceses
Ca and Vitamin D are intimately linked together in terms of uptake and function in the body

absorption of Ca affected by
Vit D
gastric Acid (makes more soluble)
lactose
citrate, malate,
protein, phosphorous
exercise

inhibited by
oxalic acid, phytic acid, dietary fiber
phosphate (binds to metals, makes insoluble)
steatorrhea (soaps)
too much fat getting past small intestine and sweeping stuff out

Front 422

calcium deficiencies

Back 422

rickets, osteomalacia (adult rickets) both reversible with supplements
vitamin D prevents ricekts (poor intestinal absorption/poor kidney reabsorption of Ca and Phopshate
osteoporosis (problems taking up and mobilizing Ca)
adult males should consume 1000mg/day, adolescents and women needmore
excessive intake increases risk of renal stone formation (genetic component)

Front 423

Phosphorous P (phosphate PO4)

Back 423

second most abundant mineral in body
85% in bones and teeth, 15% elsewhere (including nucleic acids)
also regulated by vitamin D
functions in structure of nucleic acids, phospholipids, activation of enzymes by phosphorylation, energy ATP
also acid-base balance (has many ionizable groups)

dietary sources
animal protein, milk, eggs
processed foods
food additive for pH adjustment, to sequester some things (like metals)
prevents bacterial growth
recommended intake 700-1250mg/day
dietary excess is commong, promotes Ca excretion

Front 424

Magnesium

Back 424

bone strength
ATP hydrolysis (stabilizes 3- charge of phosphate)
most bases floating around cells have an Mg on them
Enzyme cofactors (also for structural reasons) almost every enzyme in DNA/RNA reactions require Mg
binds nucleic acids directly and changes their shape
muscle relaxation after contractions
food sources
vegetables, nuts, legumes
30-50% of intake is absorbed
Intracellular>extracellular

deficiency
rate except with alcoholics (DTs, hallucinations)
hypertension, vascular disease, preeclampsia, osteoporosis
excess: anesthetic effects and diarrhea

Front 425

Sulfur S (sulfate SO4)

Back 425

sulfate in tissues and sulfur containing amino acids methionine and cysteine

key role in protein structure (Cys-S-S-Cys) disulfide bonds
involved in post-translational modification

key role in transfer gorups (acetyl CoA) things are easily attached to and removed from S

also critical in glutathione (SH a powerful tool)

no issue with def./excess as long as have normal diet

Front 426

iron

Back 426

key role in many enzymes
ETC
-complexes 1,2,3,4, iron in form of single iron atoms, iron-sulfur center that spontaneously form, iron sitting in heme and cytochromes
can transfer electrons
can bind oxygen
can catalyze reactions and do many things depending on its surroundings
transition metals, especially iron, are the molecular equivalent of nuclear fuel

iron and manganese are critical to body, but can be poisonous
can react with oxygen and make superoxide
reduced form can interact with hydrogen peroxide and make a hydroxyl radical (free radical with unpaired electron)
can destroy anything they touch
some enzymes make these on purpose

these metals can also be used to protect
catalase-destroys hydrogen peroxide (has heme in it)

Fe is redox active
can transfer electrons either way

Fe2+/Fe3+
reduction potential is the relative ability to give or accept electrons
the more negative, the more likely it will give up electrons, the more positive the more likely it will accept

redox midpoint potential, way to estimate an enzyme's ability to bind a substrate
electrical potential at which molecule is 50% oxidized and 50% reduced
cells use transition metals because they can be easily moved from one oxidation state to another without giving dangerous free radicals (due to d orbitals)
cant do this with organic molecules

Cytochrome A,C,B1 all contain iron
dramatic difference in reduction potential

Cytochrome F (.365mv) vs ferridoxin (-.432mv)
key point: proteins can grab a metal and by controlling surrounding organic elements (for example, embedded in heme prosthetic group or iron-sulfur center with different amino acids) they can tune it to whatever potential they want with same metal

can have iron at multiple potentials by controlling AAs around it
this is how ETC works
Flavins are organic rings that take up and give electrons
same flavin can have different potentials depending on what proteins are around them
main function of iron is redox chemistry

average 3-4g iron in body (half in blood via iron atom in hemoglobin)
stored as ferritin or hemosiderin

ferritin is a huge globe of many different monomers
hollow shell that contains blocks of oxidized iron
sequestering away from oxygen so that it doesnt react with oxygen and form reactive oxygen species

hemosiderin
mostly in liver, doles it out as necessary depending on blood concentration
males store about a gram, females less

iron overload
40-50g, mostly liver, spleen, bone marrow

myoglobin in muscle stores iron

ETC enzymes only 8mg to run enzymatic machines in cells (most is stored or used to transport oxygen)
strictly regulated

iron metabolism
Fe2+ is normal form, Fe3is very insoluble
reduction is activated by vitamin C
iron reaches plasma and is carried by transferrin
cells that need iron put a transferring protein receptor on surface
cells pick it up and store it as ferritin

iron can be stored in bone
every cell needs it
RBC huge amounts
reticular endothelial sells use it well

loss
liver sweeps iron into feces with bile salts
sweat
losing skin
bleeding


intestinal absorption
divalent metal transporter (DMT)
-transports many different metals
enzymes are blind that feel for certain structure
metals have similar overall shape, so they arent really differentiated by transporter
much is unknown about metal uptake in cells
taken up in 2+ form, also taken up as heme and citrate
once in intestinal cells, most will be stored as ferritin
ultimately shipped to blood stream on transferrin

iron at least 8mg per day to maintain stores since we lose about 8mg per day
RDAs higher when developing
females need more after menstruation ends and more during pregnancy for fetal development
genetically may be individual needs, we are unaware

iron uptake by transferrin
when cells have transferrin receptor on the surface, they bind the transferrin, then release iron by acidification in lysosomes
iron is then grabbed by internal proteins for storage

some metals are soluble in high acid, so easier to access in acidic condition

non-heme iron uptake
diet affects uptake
organic acids from plants, phytic acids
polythenols
-i.e. resveratrol
-have lots of OH that can grab metals, coordinate them and sweep them up in your diet

black tea and cocoa
bind iron tightly
drink lots of black tea, wash iron from diet

can stimualte uptake
Vitamin C
organic acids (i.e. citric acid)
heme

Front 427

iron excess

Back 427

hereditary defects
hemochromatosis
despite rarity, will see these in testing
iron overload

dietary overload is hemosiderosis
fad diet or heavy consumptoon of red wine or overdose of iron supplements
huge amount of oxidative stress
extra iron reacts with oxygen in body
some tissues are more sensitive (cardiac issues)
frataxin protein controls Fe levels in mitochondria
friedrich's ataxia-defective frataxin, buildup of iron in mitochondria
excess also decreases absorption of hormones and antibiotics

moderately high levels might be bad, body will try and maintain concentration at vigorous levels
infecting bacterium has no available iron
some bacterium cause hemolysis to release iron because they need it

Front 428

iron deficiency

Back 428

1 billion anemic people
dietary deficiencies
infection, heliobacter
ulcers
vitamin deficiencies
since DMTs are non discriminatory, you may get lead poisoning
transporter is waiting for iron,but grabbing other metals because similar in structure
inflammation
malabsorption
first thing seen in deificiency is anemia

Front 429

Zinc

Back 429

roles in many enzymes
involved with proteins that interact with DNA (zinc fingers)
histidines or cysteines that grab on to zinc

dna is a negative nucleic acid and zinc is positive

may have been evolutionary chosen zinc over iron because not redox active (cant add and take away electrons in biological conditions)
shaped and charged like iron but doesnt cause reactive oxygen species
hard to measure because it many things,hard to discriminate from background noise
uptake/absorption
histidines, cysteines, and phytic acid bind zinc tightly and sweep into diet
metallithioneins
proteins with 10-12 cysteines
regulation of movement and storage of zine through cells

Front 430

intestinal absorption of zinc

Back 430

much is unknown
once Zn is in, metallothioneins bind to them
might be specific transporters in blood, serum albumin may carry it as well

Front 431

zinc storage

Back 431

couple of grams, women less than men
turnover takes about a year, but estimated 1mg lost per day (skin loss)
liver turnover is faster
homeostasis regulates Zn levels in a tight range

Front 432

zinc deficiency

Back 432

take about 10mg/day
many enzymes require zinc
tissue damage, increase oxidative stress, immune deficiencies, developmental changes, skin lesions,

children develop later, not enough zinc for regulatory proteins that control cellular development
later onset of secondary sex characteristics

poor appetite (zinc linked to taste)
malabsorption diseases affect all minerals (i.e. IBS)

Front 433

zinc excess

Back 433

common belief zinc is a cure all
excess: nausea (50mg can have emetic effect)
because of DMT, too much of any mineral can affect others (ie iron and copper)
implicated in alzheimer's disease
can lower HDLs and increase cholesterols in bloodstream

Front 434

copper

Back 434

critical for complex 4- terminal oxygen reducer in ETC
has two ox states, 1+ and 2+
reduced copper is insoluble
implicated in prions and mad cow disease (bovine and human spongiform encephalopathy)
actual protein binds copper

deficiency can lead to anemia
copper uptake is linked to Fe uptake
if copper is deficient, Fe uptake is also deficient, leading to anemia
Deficiency: anemia, leukopenia, neutropenia, osteoporosis, seen in total parenteral nutrition (TPN)
excess can also cause anemia, indirectly. if you limit copper uptake, you limit iron uptake
excess: weakness, tremors

genetic diseases
wilson's disease (like hemochromatosis)
lvier cant get rid of copper, there is a buildup
early brain damage from ixidative stress, involuntary movements, psychoses, general liver damage, cirrhosis
classic greenish-gold ring in cornea from copper buildup
liver transplant or copper binding drugs

Front 435

iodine

Back 435

not really metal
critical to thyroid hormone - growth development, metabolism
micrograms per day
concentrated in thyroid
covalently bound to tyrosines in proteins
regulates metabolic rates
deficiencies: spontaneous abortion, irreversible brain damage
symptom in adult (goiter, enlarged thyroid)

excesses, no apparent effects, but can disrupt thyroid function like deficiency at chronic excess
most table salts have iodine

Front 436

selenium

Back 436

not an antioxidant, but involved in antioxidant processes
critical component of posttranslation modification of proteins (selenomethionine and selenocysteine)
similar electron shell to sulfur, but selenium is different enough to use it instead of sulfur for certain purposes (usually with proteins that have antioxidant defense)
excess: deposits into all sulfur proteins, when not every protein can use selenium in place of sulfur
adults require 55ug/day
deficiencies
-cardiac failure (sensitive to oxidative stress bc many mitochondria)
liver problems
cancer
atherosclerosis
hair loss (skin changes)

dermatitis seen in both excess and deficiency

peripheral neuropathy in excess

uptake is not well understood, hard to study because so little of it

Front 437

synthesis, processing, secretion VLDL

Back 437

Apo B100 protein (attached to lipoprotein) are synthesized on RER
Triacylglycerol (TGs) are synthesized on SER and/or on FA synthase in cytosol
TG and proteins are packaged in the Golgi complex to form VLDL
VLDL are transported to cell membrane in secretory vesicles and secreted by exocytosis
cholesterol located near surface because has OH group and is amphipathic

Front 438

Apo B100 and Apo B48

Back 438

made from same genes
Apo B100 found in VLDL and synthesized in liver, twice as long as ApoB48
Apo B48 found in chylomicrons and synthesized in intestinal cells
Different transcripts due to RNA editing
Apo B48 has UAA instead of CAA (introduces stop codon in intestinal cells)

VLDL major component is TG (not as much as chylomicrons)
epithelial cells lining gut will be packaging up the chylomicrons
go out into bloodstream
find an enzyme on lumen side of blood vessel called lipoprotein lipase
LPL takes off FA from VLDL, FA go into adipose and packaged as TGs and stored


Glucose comes in to make backbone of VLDL, Glycerol-3-P, which combines with FA CoA to make TG, which are then packaged as VLDL
VLDL meets LPL, breaks down TG to FA and glycerol and goes into adipose, becomes again TG

LPL works on chylomicrons and VLDL (both have pool TGs)

LPL is dependent on insulin

adipose only has one path to Glycerol-3-Phosphate via glucose to prevent futile cycle of TG synthesis and breakdown
insulin stimulates transport of glucose into adipose cells and stimulates synthesis and secretion of LPL

ApoCII obtained from HDL activates LPL (present on both VLDL and chylomicrons)

FA to TG in liver, sent into blood as VLDL

Acetyl CoA carboxylase regulated enzyme

Front 439

total cholesterol (TC)

Back 439

should be less than 200 mg/dL

formula is TC=HDL + LDL + (TG/5)

Front 440

TG

Back 440

refers to chylomicrons and VLDL on tests

Front 441

chylomicrons

Back 441

dietary, produced by cells lining small intestine

80% TG

Front 442

VLDL

Back 442

synthesized in liver
increase TG approximately
45% TG

Front 443

LDL

Back 443

carriers cholesterol to tissue
a lot of cholesterol

Front 444

HDL

Back 444

reverse transports cholesterol to liver
composed of more proteins compared to other constituents

Front 445

lipoproteins and transport

Back 445

Lipids (TG, FA)
chylomicrons transport from intestines to tissues
VLDL transports from liver to tissues
adipose to muscle and liver by FA on albumin in blood

cholesterol
to tissues by LDL
from tissues by HDL

Front 446

structure of lipoprotein

Back 446

apoproteins (binding things together, some towards center some out to liquid environment
amphipathic liquids
both charged and non charged parts

phospholipids have charge
some come in contact with liquid environment
some extends into center that is less charged

cholesterol - OH group
not esterified. doesnt have an FA attached to it

non polar lipids
located on the inside of the phospholipid

cholesterol esters - attached to LCFA
TG=no charge

Lipoproteins are different sizes
chylomicrons are huge
then VLDL
then LDL
then HDL

Front 447

Apo A1

Back 447

associated with HDL
activates LCAT/PCAT (same thing) in order to take cholesterol to cholesterol ester

ligand for HDL receptor

chylomicrons

Front 448

ApoB100

Back 448

LDL, VLDL, IDL

LDL receptor ligand

Front 449

ApoB48

Back 449

chylomicrons, chylo remnants,

chylo assembly and secretion, dietary lipids

Front 450

ApoCI

Back 450

VLDL, HDL, Chylomicrons
may activate LCAT
may inhibit hepatic uptake of chylo and VLDL remnants

Front 451

APO CII

Back 451

VLDL, HDL, Chylomicrons

Cofactor, activates LPL, is transferred between HDL and VLDL/chylomicrons

Front 452

ApoCIII

Back 452

VLDL, HDL, CHylomicrons

Front 453

ApoE

Back 453

VLDL, HDL, CHylomicrons, chylo remnants, LDL

hepatic receptor ligands for chylomicrons and LDL

is recycled between HDL and VLDL/chylomicrons

Front 454

both ApoB100 and ApoB48 encoded by same gene

Back 454

apoB100 attaches to LDL receptor
Deamination step whic changes the RNA by RNA editing from a C to a U changing CAA (gln) to UAA (stop)

ApoB48 codes first half of transcript

liver cells do not synthesize deaminase, so the resulting transcript and protein are longer than in intestinal cells. Apo B100 is about twice as long as ApoB48 and will attach to LDL receptor

ApoB48 will not

Front 455

Apo A1

Back 455

associated with HDL
activates LCAT/PCAT (same thing) in order to take cholesterol to cholesterol ester

ligand for HDL receptor

chylomicrons

Front 456

ApoB100

Back 456

LDL, VLDL, IDL

LDL receptor ligand

Front 457

ApoB48

Back 457

chylomicrons, chylo remnants,

chylo assembly and secretion, dietary lipids

Front 458

ApoCI

Back 458

VLDL, HDL, Chylomicrons
may activate LCAT
may inhibit hepatic uptake of chylo and VLDL remnants

Front 459

APO CII

Back 459

VLDL, HDL, Chylomicrons

Cofactor, activates LPL, is transferred between HDL and VLDL/chylomicrons

Front 460

ApoCIII

Back 460

VLDL, HDL, CHylomicrons

Front 461

ApoE

Back 461

VLDL, HDL, CHylomicrons, chylo remnants, LDL

hepatic receptor ligands for chylomicrons and LDL

is recycled between HDL and VLDL/chylomicrons

Front 462

both ApoB100 and ApoB48 encoded by same gene

Back 462

apoB100 attaches to LDL receptor
Deamination step whic changes the RNA by RNA editing from a C to a U changing CAA (gln) to UAA (stop)

ApoB48 codes first half of transcript

liver cells do not synthesize deaminase, so the resulting transcript and protein are longer than in intestinal cells. Apo B100 is about twice as long as ApoB48 and will attach to LDL receptor

ApoB48 will not

Front 463

synthesis, processing, secretion VLDL

Back 463

Apo B100 protein (attached to lipoprotein) are synthesized on RER
Triacylglycerol (TGs) are synthesized on SER and/or on FA synthase in cytosol
TG and proteins are packaged in the Golgi complex to form VLDL
VLDL are transported to cell membrane in secretory vesicles and secreted by exocytosis
cholesterol located near surface because has OH group and is amphipathic

Front 464

Apo B100 and Apo B48

Back 464

made from same genes
Apo B100 found in VLDL and synthesized in liver, twice as long as ApoB48
Apo B48 found in chylomicrons and synthesized in intestinal cells
Different transcripts due to RNA editing
Apo B48 has UAA instead of CAA (introduces stop codon in intestinal cells)

VLDL major component is TG (not as much as chylomicrons)
epithelial cells lining gut will be packaging up the chylomicrons
go out into bloodstream
find an enzyme on lumen side of blood vessel called lipoprotein lipase
LPL takes off FA from VLDL, FA go into adipose and packaged as TGs and stored


Glucose comes in to make backbone of VLDL, Glycerol-3-P, which combines with FA CoA to make TG, which are then packaged as VLDL
VLDL meets LPL, breaks down TG to FA and glycerol and goes into adipose, becomes again TG

LPL works on chylomicrons and VLDL (both have pool TGs)

LPL is dependent on insulin

adipose only has one path to Glycerol-3-Phosphate via glucose to prevent futile cycle of TG synthesis and breakdown
insulin stimulates transport of glucose into adipose cells and stimulates synthesis and secretion of LPL

ApoCII obtained from HDL activates LPL (present on both VLDL and chylomicrons)

FA to TG in liver, sent into blood as VLDL

Acetyl CoA carboxylase regulated enzyme

Front 465

total cholesterol (TC)

Back 465

should be less than 200 mg/dL

formula is TC=HDL + LDL + (TG/5)

Front 466

TG

Back 466

refers to chylomicrons and VLDL on tests

Front 467

chylomicrons

Back 467

dietary, produced by cells lining small intestine

80% TG

Front 468

VLDL

Back 468

synthesized in liver
increase TG approximately
45% TG

Front 469

LDL

Back 469

carriers cholesterol to tissue
a lot of cholesterol

Front 470

HDL

Back 470

reverse transports cholesterol to liver
composed of more proteins compared to other constituents

Front 471

lipoproteins and transport

Back 471

Lipids (TG, FA)
chylomicrons transport from intestines to tissues
VLDL transports from liver to tissues
adipose to muscle and liver by FA on albumin in blood

cholesterol
to tissues by LDL
from tissues by HDL

Front 472

structure of lipoprotein

Back 472

apoproteins (binding things together, some towards center some out to liquid environment
amphipathic liquids
both charged and non charged parts

phospholipids have charge
some come in contact with liquid environment
some extends into center that is less charged

cholesterol - OH group
not esterified. doesnt have an FA attached to it

non polar lipids
located on the inside of the phospholipid

cholesterol esters - attached to LCFA
TG=no charge

Lipoproteins are different sizes
chylomicrons are huge
then VLDL
then LDL
then HDL

Front 473

Apo A1

Back 473

associated with HDL
activates LCAT/PCAT (same thing) in order to take cholesterol to cholesterol ester

ligand for HDL receptor

chylomicrons

Front 474

Apo A1

Back 474

associated with HDL
activates LCAT/PCAT (same thing) in order to take cholesterol to cholesterol ester

ligand for HDL receptor

chylomicrons

Front 475

ApoB100

Back 475

LDL, VLDL, IDL

LDL receptor ligand

Front 476

ApoB100

Back 476

LDL, VLDL, IDL

LDL receptor ligand

Front 477

ApoB48

Back 477

chylomicrons, chylo remnants,

chylo assembly and secretion, dietary lipids

Front 478

ApoB48

Back 478

chylomicrons, chylo remnants,

chylo assembly and secretion, dietary lipids

Front 479

ApoCI

Back 479

VLDL, HDL, Chylomicrons
may activate LCAT
may inhibit hepatic uptake of chylo and VLDL remnants

Front 480

ApoCI

Back 480

VLDL, HDL, Chylomicrons
may activate LCAT
may inhibit hepatic uptake of chylo and VLDL remnants

Front 481

APO CII

Back 481

VLDL, HDL, Chylomicrons

Cofactor, activates LPL, is transferred between HDL and VLDL/chylomicrons

Front 482

APO CII

Back 482

VLDL, HDL, Chylomicrons

Cofactor, activates LPL, is transferred between HDL and VLDL/chylomicrons

Front 483

ApoCIII

Back 483

VLDL, HDL, CHylomicrons

inhibits LPL, may inhibit hepatic uptake of chylo and VLDL remnants

Front 484

ApoCIII

Back 484

VLDL, HDL, CHylomicrons

inhibits LPL, may inhibit hepatic uptake of chylo and VLDL remnants

Front 485

ApoE

Back 485

VLDL, HDL, CHylomicrons, chylo remnants, LDL

hepatic receptor ligands for chylomicrons and LDL

is recycled between HDL and VLDL/chylomicrons

Front 486

ApoE

Back 486

VLDL, HDL, CHylomicrons, chylo remnants, LDL

hepatic receptor ligands for chylomicrons and LDL

is recycled between HDL and VLDL/chylomicrons

Front 487

both ApoB100 and ApoB48 encoded by same gene

Back 487

apoB100 attaches to LDL receptor
Deamination step whic changes the RNA by RNA editing from a C to a U changing CAA (gln) to UAA (stop)

ApoB48 codes first half of transcript

liver cells do not synthesize deaminase, so the resulting transcript and protein are longer than in intestinal cells. Apo B100 is about twice as long as ApoB48 and will attach to LDL receptor

ApoB48 will not

Front 488

Pathway for chylomicrons (CM)

Back 488

small intestinal cell made nascent chylomicron with ApoB48 attached

composed of more TG than cholesterol

out in bloodstream ApoCII and ApoE are transferred from HDL to nascent CM

CM goes through capillaries and encounters LPL which takes TGs down to FAs and glycerol

extracellular LPL activated by ApoCII degrades TG in CM and VLDL to FAs which are taken up by adipose and resynthesized to TGs

as chylomicrons lose TGs they decrease size and become chylo remnants

CM remnants have more cholesterol esters than TGs
CM remnants no longer need ApoCII and give back to HDL
Keeps ApoE because it binds to receptor in liver which allows it to be taken up

cholesterol from CM may be used in liver to make bile or in membranes
if liver has enough cholesterol it will repackage as VLDL and send it back out

LDL binds to specific receptors on extrahepatic tissues and on the liver where they are endocytosed

Front 489

both ApoB100 and ApoB48 encoded by same gene

Back 489

apoB100 attaches to LDL receptor
Deamination step whic changes the RNA by RNA editing from a C to a U changing CAA (gln) to UAA (stop)

ApoB48 codes first half of transcript

liver cells do not synthesize deaminase, so the resulting transcript and protein are longer than in intestinal cells. Apo B100 is about twice as long as ApoB48 and will attach to LDL receptor

ApoB48 will not

Front 490

Pathway for chylomicrons (CM)

Back 490

small intestinal cell made nascent chylomicron with ApoB48 attached

composed of more TG than cholesterol

out in bloodstream ApoCII and ApoE are transferred from HDL to nascent CM

CM goes through capillaries and encounters LPL which takes TGs down to FAs and glycerol

extracellular LPL activated by ApoCII degrades TG in CM and VLDL to FAs which are taken up by adipose and resynthesized to TGs

as chylomicrons lose TGs they decrease size and become chylo remnants

CM remnants have more cholesterol esters than TGs
CM remnants no longer need ApoCII and give back to HDL
Keeps ApoE because it binds to receptor in liver which allows it to be taken up

cholesterol from CM may be used in liver to make bile or in membranes
if liver has enough cholesterol it will repackage as VLDL and send it back out

LDL binds to specific receptors on extrahepatic tissues and on the liver where they are endocytosed

Front 491

pathway of VLDL

Back 491

made in liver with ApoB100
has lots of TGs
nascent VLDL goes out into bloodstream
HDL gives it ApoCII and ApoE
goes through capillaries and encounters LPL and the TGs are broken down into FAs and gylcerol

FAs stored in adipose

VLDL decreases in size and become IDL and finally LDL

LDL gives ApoCII and E to HDL

can use ApoB100 which can go to any cell in body because every cell in bdoy had LDL receptor because they all need some cholesterol

can also go into liver because liver needs cholesterol
tissues making cholesterol based hormones especially need cholesterol

Front 492

LPL

Back 492

attach to capillary endothelial cells facing lumen of capillaries
synthesis and secretion stimulated by insulin
activated by ApoCII
implications for diabetics (Type I w no insulin, Type II isnt working well)
insulin wont be there to allow glucose to get into adipose tissue and wont be able to synthesize and bring LPL to surface

Front 493

wHSL

Back 493

HSL in the adipose
activated by glucagon stimulating the breakdown of TGs to FAs and gylcerol
FAs are needed quickly and will travel on albumin

Front 494

Chylmicrons

Back 494

made my epithelial cells
derived from dietary lipids
nascent chylomicrons have ApoB48 (then aquire ApoCII and Apo E)

become chylo remnants when TG:CHol = 1:1

AoE assists in CMRemnant docking in liver

Front 495

VLDL

Back 495

made in liver
derived from liver's synthesis of FA plus any FA from chylo remnants packaged as TG
nascent VLDL has ApoB100 and ApoCII and ApoE from HDL

Goes to IDL and LDL

ApoB100 is major apoprotein

LDL does not have ApoCII or ApoE

LDL carries cholesterol to peripheral tissues which have specific LDL receptors that recognize ApoB100

LDL receptors transport LDL into peripheral tissue via endocytosis

intracellular ACAT (acyl CoA cholesterol acyltransferase) takes cholesterol and adds LCFA to become cholesterol ester
allows it to be stored

Front 496

LDL uptake by cell receptor mediated endocytosis

Back 496

LDL particle has ApoB100 and alot of cholesterol ester

LDL receptor is being synthesized then sent to outside of cell where it is recognized by ApoB100
incorporated into vacuole
internalized
pH change so it can be broken down

Cholesterol comes out as lipid droplets
AA and FA can be used for anything
Cholesterol ester is stored to be used

Cholesterol regulates
its own synthesis via HMG-CoA Red

regulates LDL receptor synthesis

activates ACAT for storage

Front 497

ACAT reaction

Back 497

found in cytosol, creates storage form of cholesterol

cholesterol and fatty acyl CoA catalyzed by ACAT leads to cholesterol ester

Fatty Acyl CoA is attached to OH of cholesterol

cholesterol ester is nonpolar and can be stored as lipid droplet until needed

Front 498

unusual forms of LDL

Back 498

LDL is within circulation, but target is outside of circulation

in order for LDL to get to its receptor, it has to squeeze through and out into the ECM
how long it stays in ECM will determine some of the problems associated with Coronary Artery Disease

Front 499

Lipoprotein A

Back 499

LDL bound to apolipoprotein A
having too much is a risk factor for CAD
ApoA is structurally similar to plasminogen (attaches to blood clots to break them down) but no enzymatic activity

because it binds to the clots, it competes with plasminogen and prevents clot breakdown
antithrombolytic, procoagulant capacities

may not be all bad

Front 500

small dense LDL

Back 500

more artherogenic
can squeeze in easier into ECM and has tendency to stay there longer
lower binding affinity for LDL receptor
high penetration into arterial wall

Kringles-binds to clot so plasminogen digests it

Front 501

HDL

Back 501

reverse cholesterol transporter

ApoA-1 synthesis in liver and sent into bloodstrea, encounters peripheral tissue
complex interactions with ABCA-1
ABCA-1functions
-brings cholesterol out to surface so HDl can get it
-takes in ApoA-1 (there is series of rxns leading to ApoA1 coming out as nascent HDL)

becomes nascent HDL
(like flat pancake because phospholipids and cholesterol, but no non polar components to make it round

PCAT converts cholesterol to esters deriveing FA from phosphatidylcholine
-this enzyme is associated with HDL
as make more esters, it will get round

there is exchange occuring between VLDL and HDL via action of two enzymes

HDL is taking FAs off of phospholipids to make cholesterol esters
eventually it runs out of phospholipids, needs to make an exchange for new phospholipids

sometimes HDL can go right into liver through hepatic lipase or it can go past liver and give up some cholesterol in the liver and keep going

Front 502

HDL

Back 502

synthesized from liver as ApoA1 and secreted into bloodstream

transfers ApoCII and ApoE back and forth from CM and VLDL
Drives by ABCA1 to pick up cholesterol and take back to liver
called "reverse cholesterol transport) since its returning to liver
ABCA1s job is to get cholesterol out of tissue and on to outer leaflet of tissue

general functions include
antioxidant activity
inhibiting platelet activity

contains PCAT (phosphatidylcholine cholesterol acyl transferase)
enzyme that transforms cholesterol into a non polar cholesterol ester
reaction involves taking a FA off of phosphatidylcholine and transferring it to cholesterol
reaction is stimulated by apoA1
deficiency with this enzymes results in FishEye disease
-HDL not having many esters, roughly 20% of total cholesterol
patient presents with opacity in their cornea, which is dense and white, similar to eyes of boiled fish
otherwise benign

Front 503

ABCA1 loads HDL with cholesterol from tissues

Back 503

ABCA1 is ATP binding cassette 1
part of family of ~20 ABCs
function is to transport molecules in and out of tissues
one example is drugs, whether it is good or bad depends on what drug is doing in tissues
also bile transport
loads HDL with cholesterol from tissues

Front 504

Tangier Disease

Back 504

patient presents with enlarged, orange yellow tonsils
these people have very low HDL, sometimes barely any
as a result, tonsils collect a lot of cholesterol
disease state is a result of mutation ABCA1
-rare autosomal recessive disease
cannot eliminate cholesterol from tissues because ABCA1 cannot give to HDL
also ApoA1 cannot be processed into HDL

Front 505

LP exchange

Back 505

CETP-cholesterol ester transfer protein

PLTP
phospholipid transfer protein
transports molecules between HDL and VLDL
HDL can transport phopsholipids to VLDL since it has an abundance of it
essentially, enzymes are involved in remodeling of HDL

Front 506

Role of liver

Back 506

takes up chylomicron remnants
makes HDL at least the ApoA1 part
takes up HDL containing cholesterol on HDLs trip back from tissues
synthesizes cholesterol
-produces bile using some cholesterol
-secretes extra cholesterol into feces
synthesizes FAs and uses it to create VLDLs

Front 507

Cholesterol comes from Food and Family

Back 507

statin blocks major step in synthesis of cholesterol (HMG-CoA reductase)

Front 508

biosynthesis of cholesterol

Back 508

two enzymes
HMG CoA Synthase
makes HMG-CoA
(KB synthesis)
HMG-CoA synthase can make cholesterol or KBs

HMG-CoA reductase
second enzyme
makes mevalonic acid
rate-limiting step, once initiated cholesterol will be synthesized

after mevalonic acid synthesis there is a group of isoprenes
(groups of 5 carbon structures)
enzyme cyclase closes open rings and result is lanosterol
after lanosterol, you get cholesterol
cholesterol inhibits rate limiting step, HMG-CoA reductase (product inhibition)

Front 509

Regulation of HMG CoA reductase

Back 509

first, cholesterol is inhibiting a transcription factor (TF), SCREBP-2
cholesterol binds SCAP
-SCAP is attached to SCREBP2, is the precursor form of SCREBP2
binding occurs in ER, sequestering the TF there
prevents TF from getting into nucleus and inducing transcription (TS) of HMG-CoA Reductase

second event involves degradation of enzyme that makes HMG CoA reductase if sterols are present (if enough cholesterol is present)
-under such conditions, enzyme that makes HMG CoA reductase is ubiquinated and targeted for time in proteasome

third event is covalent modification by AMP-kinase which phosphorylates HMG-CoA reductase and makes it inactive
same type of regulator involved in regulation of acetyl coA carboxylase
insulin can use a phosphatase to get that phosphate off (reversing the conditions) and reactivating the enzyme

final event involves conditions of either high insulin or thyroxine or low glucagon or low glucocorticoid levels
these conditions regulate TS of HMG CoA reductase
when insulin or thyroxine is high, that telling cell that it needs HMG CoA reductase around
high glucagon or glucocorticoids says no we dont need it so downregulate it

Front 510

high cholesterol can sneak up on you

Back 510

shows that liver loads fat onto VLDLs which travel through blood and later become LDL
LDL cholesterol may become stuck as travels through blood, sticking to blood vessel wall
HDL take pieces of LDLs back to liver where cholesterol can be repackaged
if too much cholesterol in blood, not enough HDL to sequester, can cause blockage and heart attack

Front 511

atherosclerosis

Back 511

over time, plaque builds up in blood vessels
eventually, a blood clot has formed and blood vessel is closed off
LDL must squeeze through endothelial cells to get to tissues
LDLs can be oxidized and stuck in blood vessel walls
oxidants can be superoxide, nitric oxide, hydrogen peroxide
once oxidized, LDL cannot go back into bloodstream

stuck LDLs are phagocytized by monocytes that become macrophages, macrophages take up LDL by two receptors
high affinity and non specific receptor

become foam cells
start accumulating along blood vessel walls
contributes to plaque buildup though they are trying to eliminate oxidized LDL

lots of calcium=more stiff plaque buildup

Vitamin E, ascorbic Acid, Beta-carotene prevent oxidation
bilirubin might help as well

Front 512

coronary artery disease equivalents

Back 512

precursors that lead to it
-diabetes
-aortic aneurysm
-peripheral vascular disease
-carotid artery disease (stroke, transient ischemic attach)

Front 513

framington risk equation

Back 513

age for men is different than women, partially because of menopause
women have higher age before theyre at risk because of estrogen

Front 514

metabolic syndrome

Back 514

step 8 of ATPIII

considered to have metabolic syndrome if have three of following

abdominal adiposity/obesity
high blood pressure
hypertriglycerides (VLDLs, LDLs, Chylomicrons, low HDL)
Fasting hyperglycemia
inflammatory signs (likely due to microalbuminurea caused by albumin excretion through kidneys

metabolic syndrome can be reversed to some degree

Front 515

vertical auto profile

Back 515

conducted occasionally
can have HDL2 or 3 (2 is more protective)
can have LDL A or B (difference not specified)
Therefore total amount may not be indicative of good thing

Front 516

CHD risk factors

Back 516

similar to ATP III
positive (bad) risk factors include
male>45, female>55yrs or premature menopause
premature coronary artery disease in close relatives
smoking
hypertension
HDL under 35 mg/dL
diabetes
obesity
HDL above 60mg/dL is negative (good) risk factor)
can counteract positive risk factor
rsik factors have geometric rise (exponential)

Front 517

LDL cholesterol based on risk category

Back 517

LDL under 100 in general
if have low risk, LDL below 160
Moderate risk, LDL below 130
High risk, LDL below 100
beign with therapeutic life changes, dont jump right into drug therapy

Front 518

for high risk patients, ATPIIIconsders keeping LDL below 100 a minum goal, NIH below 70

Back 518

really hard to do, talk about giving everyone lipitor

Front 519

why hyperlipidemia

Back 519

smoking (risk for atherosclerosis)
high fat diet
diabetic
obese
hypertensive, high stress in life
homocysteine is separate risk factor (if not due to genetic deficiency, then due to low folate and/or vitamin b12 levels (or even low vitamin B6 levels)
biggest challenge is patient compliance

secondary causes include pregnancy (hypercholesteremia)
diabetes (hyperglyceridemia)

Front 520

genetic causes of hyperlipidemia

Back 520

LDL receptor def., LDL in bloodstream, cholesterol in bloodstream

abnormal ApoE, more chylomicrons, CM remnants

increased synthesis VLDL with decreased breakdown, then VLDL, TGs, lipids increas free

no LPL activity or are ApoCII deficient

cant break down CMs and VLDL, more TGs in blood

Front 521

Tx approaches

Back 521

statin is number one
inhibits HMG-CoA reductase
six different kinds of statins
side effects include having to monitor liver health/get tests

bile acid sequestrants
-bile acid is made from cholesterol and goes into intestine to coat lipid droplets in diet
helpful with incorporating lipids into cells
bile acids are usually recycled, but a bile acid sequestrant blocks this
instead they are eliminated into feces
body now has to make more bile, thus it pulls cholesterol from bloodstream in order to do so
side effects include bloating, constipation, triglycerides increase side effects

fibric acid/fibrates
ligands of ppar-alpha (peroxisome proliferator activated receptor)
increases LPL expression, lowers VLDL
-especailly a good thing if have high triglycerides
no so well if have high cholesterol
side effects include myopathy if combined with statins

niacin/nicotinic acid
mechanism not known
one of bodys vitamins
100x dose of RDA
side effects (flushing etc)

ezetimbe
second part of vytorin
keeps lipids fom being absorbed into diet

omega 3s
PUFA, inhibit TG synthesis
raises HDL

Front 522

vitamins

Back 522

cannot be synthesized by organism in amount sufficient for physiological needs

absence can cause specific deficiency syndromes

Front 523

early 20h century funk purified thiamine, B1 from rice polishing

Back 523

cured beriberi

Front 524

ancient egyptian writings as old as 1500 BC record that liver consumption cured night blindness

Back 524

1747 british physicailn lind discovered that acidic citrus fruits could miraculously cure scurvy

1855 japanese sailors ate polished rice and suffered from beriberi, cured by supplementing with diet of meat, milk, vegetables

Front 525

13 vitamins essential for humans
vitamins play many roles in metabolism

Back 525

typically used as cofactors for enzymes
-cofactors do post translational modifications to extend range of chemistry that can happen in cell

-coenzymes--are attached to enzyme as prosthetic groups, or considered cosubstrates (like NAD)

vitamins are organic

Front 526

essential nutrients

Back 526

conditionally essential nutrients (choline, lipoic acid, ubiquinone, taurine)

non-essential (that also confer health benefits)
-flourine to stabilize teeth
-flavonoids for antioxidants, phytoestrogens, carotenoids for antioxidants

Front 527

most rapidly dividing cells are ones effected by vitamin deficiency

Back 527

anemia (macrocytic, microcytic)
skin problems
CNS problems (BC energy is so critical)

Front 528

fat soluble vitamins

Back 528

A D E K

Front 529

NIacin

Back 529

coenzyme is Nicotinamide Adenine Dinucleotide or Nicotinamine Adenine Dinucleotide Phosphate

Redox reactions involving two-electron transfers

Front 530

Riboflavin

Back 530

B2
Flavin Mononucleotide
Flavin Adenine DiNucleotide

one or two electron transfers Redox

Front 531

Pantothenate

Back 531

B3
Coenzyme A
Transfer of acyl groups

Front 532

Thiamine

Back 532

Thiamine Pyrophosphate TPP
transfer of two-carbon groups containing a carbonyl

B1

Front 533

pyroxidine

Back 533

Pyroxidal Phosphate (PLP)
B6
Transfer of groups to and from AAs

Front 534

Biotin

Back 534

Biotin
ATP dependent carboxylation of substrates or carboxyl group transfer between substrates

Front 535

Folate

Back 535

tetrahydrofolate
transfer of one carbon substituents
especially formyl and hydroxymethyl groups, provides methyl group for thymine in DNA

Front 536

Cobalamin

Back 536

B12
Adenosylcobalamin
intramolecular rearrangements
Methylcobalamin
transfer of methyl groups

Front 537

vitmin A

Back 537

retinal, vision

Front 538

vitamin K

Back 538

vitamin K
carboxylation of glutamate residues

Front 539

inositol

Back 539

for phospholipids
a sugar alcohol with 6 OH groups
important for cell signaling, part of membrane glycoproteins

Front 540

Choline

Back 540

in phospholipids, methyl donor, has been demonstrated that healthy men on choline free diet develop liver damage

Front 541

lipoic acid

Back 541

required for pyruvate decarboxylase, animals can make this

Front 542

PQQ

Back 542

pyrroloquinoline quinine (methoxatin)
a redox cofactor for quinoproteins (flavoproteins, dehydrogenases

Front 543

Vitamin D

Back 543

synthesized when in sunlight