Biochemistry Exam 3

Front 1

Acetyl-CoA Carboxylase

Back 1

rate limiting step of fatty acid biosynthesis
catalyst for the rxn of Acetyl-CoA + HCO3 --> Malonyl CoA
Reaction is irreversible

Front 2

3 Parts of Acetyl CoA Carboxylase and 2 steps of rxn

Back 2

3 Parts:
Biotin carrier protein
biotin carboxylase
transcarboxylase
2 Steps
biotin carboxylation from ____
Carboxyl transfer from ___ to ___

Front 3

Acetyl-CoA Carboxylase Regulation

Back 3

Feedback Inhibitor: Palmitoyl-CoA
Citrate: Allosteric Activator triggered by inc. conc of mitochondrial acetyl-coa and ATP. At the same time, citrate will inhibit phosphofurctokinase-1 (glycolysis)
Covalent Modification: Glucagon and epinephrine inactivte the enzyme by phosporylation

Front 4

Steps before fatty acid synthesis

Back 4

KS gets acyl from acetyl coa, catalyzed by MT
ACP gets acyl from malonyl coa, catalyzed by AT

Front 5

ACP

Back 5

Acyl Carrier Protein
highly exergonic thioseter bonds that fuel the unfavorable steps of synthesis (1 and 5)

Front 6

Overview Fatty Acid

Back 6

Pre-steps:
-introduce acetyl and malonyl coa to fatty acid synthase, KS and ACP respectively
1. Condensation
2. Reduction
3. Dehydration
4. Reduction/Translocation

Front 7

Chemical Energy Required for Biosynthesis

Back 7

ATP: necessary to attach CO2 to acetyl coa and make malonyl coa
NADPH: needed to reduce the double bonds for step 2

Front 8

Step 1: Fatty acid synthesis

Back 8

Condensation:
catalyzed by Beta-ketoacyl-ACP synthase (KS)
acetyl group transferred from Cys-SH of KS to ACP
Acetyl Coa carbons are added to malonyl coa carbons on the ACP

Front 9

Step 2: Fatty Acid Synthesis

Back 9

Reduction
catalyzed by beta ketoacyl-ACP reductase (KR)
Requires NADPH + H --> NADP+ for energy
Reduces C-3 double bond with O

Front 10

Step 3: Fatty Acid Synthesis

Back 10

Dehydration
catalyzed by beta-hydroxylacyl-ACP dehydratase (HD)
Water is removed from C-2 and C-3

Front 11

Step 4: Fatty Acid Synthesis

Back 11

Reduction
Catalyzed by enoyl-ACP reductase (ER)
NADPH + H --> NADP+ required for energy
Double bond C-2 C-3 removed to form saturated carbon chain

Front 12

Step 5: Fatty Acid Synthesis

Back 12

Translocation
Butyryl group is moved from ACP to Cys on KS enzyme so that it can go through pathway again.

Front 13

4 catalyst in synthesis

Back 13

1. Beta ketoacly-ACP synthase KS
2. Beta ketoacyl ACP reductase (KR)
3. Beta hydroxy ACP dehydructase (HD)
4. Enoyl ACP Reductase (ER)

Front 14

Palmitate Modification

Back 14

Elongation
Desaturation

Front 15

Elongation

Back 15

occures in Smooth ER
uses palmioyl CoA and malonyl CoA
Similar steps as synthesis but uses CoA catalyst instead of fatty acid synthase

Front 16

Desaturation

Back 16

Occurs in smooth ER
uses Mixed Functional Oxidase
common product is unsaturated ∆9 fatty acyl CoA
Uses stearoyl CoA from the elongation

Front 17

Physiologic controls of Acetyl CoA Carboxylase

Back 17

Palmitoyl CoA
ATP (glucagon stimulated)
Citrate

Front 18

Regulation of Fatty Acid Synthesis

Back 18

Substrate availability
Acetyl CoA Carboxylase
Allosterically--citrate and dephosphorylation
Allosterically--palmitoyl CoA and phosphorylation

Front 19

2 fates of triglycerols

Back 19

storage of energy
maintain cellular membranes

Front 20

2 precursors of triglycerols

Back 20

fatty acyl CoA and L-glycerol 3 Phosphate

Front 21

L-Glycerol 3-Phosphate

Back 21

important precursor in formation of triaclglycerols and glycerophospholipids
Mostly formed from dihydroxyacetone phosphate (DHAP) with NADH + H --> NAD+ using glycerol3 3-P dehydrogenase

Front 22

Glycerol 3-P dehydrogenase

Back 22

High in adipose
present in liver
when blood sugar level is high, the adipose tissue can convert sugar to fat

Front 23

Glycerol

Back 23

Precursor to triacylglycerol and glycerophospholipids to form glycerol 3-P
Used in the liver and kidney
via ATP dependent rxn with enzyme glycerol kinase

Front 24

Glycerol Kinase

Back 24

Adds PO3 group to Glycerol in kidney and liver to form Glycerol 3-P

Front 25

Acyl Transferases

Back 25

Enzyme catalyses first stage of triacylglycerol synthesis
Adds to acyl groups to glycerol 3-P
Product is phosphatidate

Front 26

Phosphatidate

Back 26

glycerol back bone with 2 fatty acids and 1 phosphate
Precursor for all glycerol fatty acids

Front 27

Synthesis of Phoshatidate

Back 27

Explain synthesis
where it occurs
2 precursors

Front 28

2 Major classes of Membrane phospholipids

Back 28

Glycerophospholipids
Sphingolipids

Front 29

General Structures of Glycerophospholipids

Back 29

Describe the general skeleton of glycerophospholipids:
Choline
Ethanolamine
Inositol
Serine

Front 30

Phosphatidylinositol

Back 30

Explain Synthesis: Steps and Precursors

Front 31

Cardiolipin

Back 31

Explain Synthesis: Steps and Precursors

Front 32

Synthesis for CDP-activated diacyglycerols

Back 32

Forms Cardiolipin and Phosphatidylinositol

Front 33

Synthesis for CDP-activated polar head groups

Back 33

Forms phosphatidylcholine and phosphatidylethanolamine

Front 34

Phosphatidylcholine

Back 34

Explain synthesis: Strategy 2

Front 35

Phosphatidylethanolamine

Back 35

Explain synthesis: Strategy 2

Front 36

Methylation of Polar Head Group

Back 36

Formation of phosphaditylcholine

Front 37

Synthesis Using base Exchange

Back 37

Formation of phosphatidylserine

Front 38

Phosphatidylcholine

Back 38

Explain its synthesis from phosphatidylethanolamine

Front 39

Phosphatidylserine

Back 39

Explain its synthesis froom phosphatidylethanolamine

Front 40

4 step synthesis of sphingolipids

Back 40

1. synthesis of sphinganine
2. attachment of fatty acid to yield N-acylsphinganine
3. desaturation to form ceramide
4. Attachment of head group to yield glucosylceramide or sphingomyelin

Front 41

Sphingosine

Back 41

product of palmitoyl-CoA + Serine
Rxn requires energy from NADPH and FAD and releases CO2

Front 42

Ceramide

Back 42

Major intermediate of Sphingolipid formation
Formed in second step of synthesis
Sphingosine + Acyl-CoA --> ceramide

Front 43

2 Types of sphingolipid

Back 43

Glucosylceramide (aka-Cerebroside )
Sphingomyeline

Front 44

5 Types of glycerophospholipids

Back 44

Phosphatidylinositol
Cardiolipin
Phosphatidylethanolamine
Phosphatidylcholine
Phosphatidylserine

Front 45

Glucosylceramide

Back 45

Sphingolipid formed from ceramide and head-group sugar attached to C-1 from UDP sugar

Front 46

Sphingomyelin

Back 46

ceramide + phosphatidylcholine--> sphingomyeline
Phosphatidylcholine serves as the donor of phosphocholine, rather than CDP-choline

Front 47

Degredation of Glucosylceramide

Back 47

Breakdown of Glucosylceramide by Glucocerebrosidase yields Glucose and ceramide

Front 48

Niemann-Pick

Back 48

sphingomyelinase defiency
causes accumulation of sphingomyelin

Front 49

Gaucher

Back 49

Glucocerebrosidase deficiency
Causes accumulation of glucosylceramide

Front 50

Tay-Sachs

Back 50

Hexosaminidase A deficiency
Causes ganglioside GM2 accumulation

Front 51

Eicosanoids

Back 51

Prostaglandins, PGE2
Thromboxanes, TXA2
Leukotrienes, LTA4

Front 52

Eicosanoid Synthesis:

Back 52

What is precursor? Arachidonic acid
What are major enzymes?
COX, Lipoxygenase, peroxidase activity of COX

Front 53

Cholesterol Synthesis

Back 53

What are 4 steps

Front 54

Stage 1 of Cholesterol synthesis

Back 54

What is rate limiting step
What are major enzymes

Front 55

HMG-CoA Reductase

Back 55

Membrane protein of smooth ER
What reaction does it synthesize?
What is energy requirement.
Is it rate limiting

Front 56

Stage 2 of Cholesterol Synthesis

Back 56

Formation of Isoprene Unit
∆3 isopentenyl pyrophosphate can be isomerized to dimethylallyl pyrophosphate and this is used in stage 3

Front 57

Stage 3 of cholesterol synthesis

Back 57

products of stage 2, isopentenyl and dimethylallyl are used to form squalene
isopentenyl + dimethylallyl --> geranyl (10C) + isopentenyl --> farnesyl (15C)+ farnesyl --> squalene (30C)

Front 58

Prenyl transferase

Back 58

enzyme in stage 3 of cholesterol synthesis

Front 59

squalene synthesase

Back 59

enzyme of stage 3 of cholesterol synthesis

Front 60

Stage 4 Cholseterol synthesis

Back 60

conversion of squalene to the four ring steroid nucleus

Front 61

Squalene synthase

Back 61

requires NADPH and produces squalene in head-to-head synthesis

Front 62

cyclases

Back 62

squalene epoxide cyclic to form lanosterol

Front 63

lanosterol

Back 63

Formed in stage 4 of cholesterol synthesis and has characteristic 4 ring structure

Front 64

Cholesterol Synthesis enzymes

Back 64

HMG CoA synthase
HMG CoA reductase
Squalene Synthase
lanosterol cyclase: 2,3 oxidosqualene
7-dehydrocholesterol reductase

Front 65

HMG CoA synthase

Back 65

Cytoplasmic, which is diff from mitochondrial enzyme which forms ketone bodies
catalyzes production of HMG CoA

Front 66

ACAT

Back 66

Acyl-CoA: cholesterol acyltransferase
cholesterol + Acyl CoA --> cholesteryl ester + CoA
Storage in the cell as lipid droplet; incorporation into lipoproteins

Front 67

LCAT

Back 67

lecithin: cholesterol acyltransferase
cholessterol + phosphatidycholine --> cholseteryl ester + lysophosphatidylcholine
storage in the blood as lipoprotein

Front 68

Plasma lipoproteins

Back 68

Chylomicron
VLDL
HDL
LDL

Front 69

HDL

Back 69

Mostly apoprotein
contains LCAT; forms cholesteryl esters from cholesterol

Front 70

Chylomicrons

Back 70

movement of lipids from large intestine to other body parts
remenants are taken up by liver
Has most amount of triglycerols

Front 71

VLDL

Back 71

delivers endogenous lipids and cholesterol from liver to the muscle and adipose tissue
removal of triacylglycerol from VLDL eventually converts them to LDLs

Front 72

LDL

Back 72

low density lipoprotein
very rich in cholesterol and cholesteryl esters
carry the cholesterol to extrahepatic tissue that has specific plasma membranes

Front 73

HDL

Back 73

originates in liver and smal intestine as small protein rich particle with little cholesterol and contain LCAT
can be taken up in the liver but also delivers to other tissue

Front 74

Apoliproteins

Back 74

ApoA--HDL; activator of LCAT
ApoB 100--VLDL, LDL; ligand for receptor, structural role
Apo 48--chylomicron; structural
Apo C-11--chylomicron, VLDL, HDL; activator of lipoprotein lipase
Apo E--chylomicron, VLDL, apoE rich HDL; ligand for receptor

Front 75

Enzymes for lipoprotein metabolism

Back 75

LCAT
LPL
HL
Acid Lipase

Front 76

Lecithin: cholesterol acyltransferase

Back 76

phosphatidylcholine and cholesterol are the substrates and occurs in lipoproteins especially nascent HDL

Front 77

Lipoprotein Lipase (LPL)

Back 77

substrates are triacylglycerol in VLDL and chylomicron and it occurs on capillary surfaces

Front 78

Hepatic lipase (HL)

Back 78

Triacylglycerol stubstate and phospholipids in IDL and HDL and occurs in the liver sinusoids

Front 79

Acid lipase

Back 79

uses triacylglycerol and cholesteryl esters and occurs in lysosomes

Front 80

Know plasma transformations of lipoproteins

Back 80

chylomicron---->chylomicron remnant (small intestine to liver)
VLDL ---> LDL (liver to liver and extrahepatic tisssue)
HDL ---> apo-e rich HDL (small intestine to ?)

Front 81

Fat utilization and regulation

Back 81

not all organs can directly use fat or fatty acid
The liver has major role in fat usage and production

Front 82

Role of liver in fat regulation

Back 82

provides supply of glucose to other systems
regulates blood glucose by conversion to and from glycogen
can produce glucose from other materials like lactate
will make fatty acid when there is excess glucose and glycogen
makes ketone bodies for other organs

Front 83

Chylomicrons

Back 83

largest lipoprotein
movement of triacylglycerols

Front 84

VLDL

Back 84

carry triglycerols and and some cholesterol

Front 85

LDL

Back 85

very rich in cholesterol and cholesterol esters
removal of triacylglycerol from VLDL produces low density lipoprotein

Front 86

Liver after meal

Back 86

After a meal: glucose from blood ---> glycogen and fatty acid synthesis sends VLDL to adipose tissue

Front 87

Liver after fasting

Back 87

After fasting: glycogen breaks down to send glucose to blood
fatty acid from adipose tissue is used as fuel in liver

Front 88

Adipose tissue major points

Back 88

fatty acids are transported from liver to fat as VLDL complexes
fatty acid are then reconverted to triglycerides in adipose cell for storage
glycerol-3P is required by cell to make triglycerides. this must come from glucos
we don't store fat without excess glucose

Front 89

Muscle tissue fxn

Back 89

at rest: energy from b-oxidation of fatty acid
at work: internal glycogen, builds up lactate
alanine can be produced
Alanine and lactate are shipped to liver for conversion

Front 90

Pentose phosphate pathway

Back 90

fermentative pathway (no O2 required)
not very energy yielding
2 major products:
ribose 5 phosphate (for nucleotide synthesis)
NADPH (for biosythetic reactions and antioxidant reducing)
used in cells that are rapidly dividing like bone marrow, skin, intestinal mucosa, used to make RNA, DNA, and enzylmes like ATP, NADH, FADH2 and coenzyme A

Front 91

Oxidative and non oxidative phases

Back 91

oxidative: produces NADPH and ribose 5 phosphate
non oxidative: takes 1 ripose-5P and 1 xylulose-5P and rearranges back to glucose-6P to continue with oxidative phase
only occurs in tissues which NADPH is needed in high amounts

Front 92

Where PPP occurs--needs ribose 5 phosphate

Back 92

tissue that needs lots of ribose 5 phosphate
rapidly dividing:
bone marrow, skin, intestinal mucosa, tumors
--->ONLY needs oxidative

Front 93

Where PPP occurs--needs lots of NADPH

Back 93

cells synthesizing fatty acid, cholesterol, steroid:
liver, adipose, lactating mammary, adrenal cortex, gonads
cells exposed to high level oxygen:
erythrocytes, cornea and lens
--->BOTH oxidative and non oxidative steps

Front 94

Hexokinase/glucokinase

Back 94

catalyzes:
glucose---> Glucose 6-P

Front 95

oxidative in PPP

Back 95

produces pentose phosphates and NADPH
4 steps:
2 involve dehydrogenase reactions that produce NADPH

Front 96

nonoxidative in PPP

Back 96

produces Ribose 5-P AND NADPH

Front 97

Glutathione/NADPH

Back 97

important in protecting cells from highly reactive oxygen derivatives
Glutathione (GSH) is tripeptide of GLU, CYS and GLY
H+ donor for proteins that have been oxidized

Front 98

Oxidative phase Step 1

Back 98

glucose 6-P ---> 6-Phospho-glucono-lactone
Catalyzed by glucose 6-Phosphate dehydrogenase
NADP+ ---> NADPH + H+

Front 99

Glucose 6-Phosphate Dehydrogenase

Back 99

catalyst of oxidative phase step 1 glucose 6-P --> 6-phospho-glucono-lactone
Produces NADPH

Front 100

Oxidative phase step 2

Back 100

6-Phosphoglucono-lactone--> 6-phosphogluconate
catalysed by Lactonase

Front 101

Oxidative Phase Step 3

Back 101

6-phosphogluconate--> D-Ribulose-5 Phosphate
Catalyzed by 6-phosphogluconate dehydrogenase
Produces NADPH and releases CO2

Front 102

6-phosphogluconate dehydrogenase

Back 102

catalyzes step 3 of oxidative phase
6-phosphogluconate-->D-Ribulose-5-phosphate

Front 103

Oxidative step 4

Back 103

D-ribulose-5 phosphate (ketose)--> D-Ribose-5-phosphate (aldose)
Enzyme: Phosphopentose isomerase

Front 104

D-Ribose-5-Phosphate

Back 104

final product of oxidative phase and initiates the NON-oxidative phase

Front 105

D-Ribulose-5-Phosphate

Back 105

product of step 3 oxidative
it can be shunt off to the non-oxidative phase when you need more NADPH

Front 106

Non oxidative phase

Back 106

2 enzyme transketolase and transaldolase transfer 2C or 3C ketose units to aldose acceptors
six 5 carbon compounds are converted to five 6 carbon compounds (glucose 6-P) which can re-enter PPP, enter glycolysis, be converted to glycogen, etc

Front 107

Ribose 5-phosphate epimerase

Back 107

ribulose 5-P --> Xylulose 5-P

Front 108

Transketolase Reaction

Back 108

transfer of 2 carbon ketose group to an aldose receptor
just rearranging the carbons
Requires TTP cofactor
catalyzes rxn from 2 Five carbons --> 7C and 3C

Front 109

Wernicke-Korsakoff syndrome

Back 109

caused by mutation in transketolase and deficiency in thiamine

Front 110

Nonoxidative step 2

Back 110

xyulose 5-P + ribose 5-P --> glyceraldehyde 3-P + sepdoheptulose 7-P
Catalyzed by transketolase/TPP cofactor

Front 111

Nonoxidative step 3

Back 111

sedoheptulose 7-P + Glyceraldehyde 3-P --> Erythrose 4-P + fructose 6-P
Catalyzed by transaldolase

Front 112

Transaldolase

Back 112

transports 2 OR 3 carbons

Front 113

Nonoxidative phase step 4

Back 113

xylulose 5-5 + erythrose 4-P --> glyceraldehyde 3-P + Fructose 6-P
catalyzed by Transketolase

Front 114

Pyruvate Dehydrogenase

Back 114

Pyruvate ---> Acetyl CoA
Highly favored; irreversible
5 co-factors:
Thiamine TPP Vit. B1
Niacin NAD+ Vit. B2
Riboflavin FAD Vit. B3
Pantothenate CoA
Lipoate (only non vitamin)

Front 115

plasma albumin

Back 115

major carrier of free fatty acid in blood
binds up to 10 mol.mol

Front 116

fatty aceyl coa synthase

Back 116

catalyst for first rxn of beta oxidation
fatty acid --> fatty aceyl CoA
After conversion, fatty aceyl coA enters the mitochondria

Front 117

ketone bodies

Back 117

d-beta-hydroxybutyrate
acetoacetate
acetone

Front 118

steps of beta oxidation

Back 118

oxidation
hydrolysis
oxidation
thiolysis

Front 119

Energy from beta oxidation

Back 119

Example 18 Carbon
Activation -2 ATP
9 Acetyl CoA (12 ATP each) = 108 ATP
8 FADH2 (2 ATP each) = 16ATP
8 NADH+ H (3 ATP each) = 24 ATP