M2C Exam 2

Front 1

Glycolysis: occurs in __________, immediate source of energy ( __ ATP in limited amounts), source of reducing equivalents in the form of _____ , ______ (raises/lowers) pH of cell; leads to two possibly pathways for the metabolized pyruvate, ___ and ____.

Back 1

occurs in cytosol; source of 2 immediate ATPs; source of reducing equivs in the form of 2NADH; lowers pH of cell; leads to two possible fates for pyruvate, either CAC under aerobic conditions or lactate under anaerobic conditions

Front 2

the CAC is also known as the _____ or the _____

Back 2

Krebbs cycle, Tricarboxylic Acid Cycle

Front 3

the CAC occurs only in the _____

Back 3

mitochondria

Front 4

the Krebbs cycle completely converts ______ to _______

Back 4

the carbon skeleton of pyruvate ----> CO2

Front 5

the CAC directly forms one ___________

Back 5

GTP

Front 6

the TCA cycle creates reducing equivs in the form of _____ and _______ ; these in turn can be converted to ATP via oxidative phosphorylation

Back 6

4 NADH and 1 FADH2

Front 7

____ is the central pathway for degradation and interconversion of carbohydrates, proteins, and fats

Back 7

the Krebbs cycle

Front 8

oxidative phosphorylation only occurs in ____________ in the presence of _______

Back 8

the mitochondria, in the presence of O2

Front 9

oxidative phosphorylation produces ATP from the ____________ produced in the TCA cycle

Back 9

reducing equivs (NADH, FADH2)

Front 10

___________ can be used for energy even in the absence of either mitochondria or O2

Back 10

carbohydrates (glucose)

Front 11

______ require mitochondria and O2 for energy production.

Back 11

protein and fat

Front 12

the Pentose Phosphate Pathway, aka the _____________, occurs in the __________

Back 12

Hexose Monophosphate Shunt, cytoplasm

Front 13

the PPP produces reducing equivs in the form of __________ , which is used for biosynthetic rxns and the production of _________, which protects cell membranes from oxidative damage

Back 13

NADPH, reduced glutathione

Front 14

the PPP can also produce ______, which is needed for nucleotide synthesis

Back 14

ribose 5-Pi

Front 15

in the __________, some carbons can be converted to pyruvate; thus, it is often referred to as as "shunt" of glycolysis

Back 15

PPP/hexose monophosphate shunt

Front 16

_______ raises blood sugar during fasting and exercise

Back 16

gluconeogenesis

Front 17

gluconeogenesis occurs primarily in the _______ and, to a lesser extent, in the _______

Back 17

liver, kidney

Front 18

gluconeogenesis can result in the conversion of both ________ and (some) _________s to glucose

Back 18

lactate, amino acids

Front 19

gluconeogenesis requires energy in the form of ________ and ________ in the form of NADH; thus it is an _________ pathway

Back 19

ATP, reducing equivs; anabolic

Front 20

_________ is the storage form of glucose

Back 20

glycogen

Front 21

glycogen metabolism occurs primarily in the ___, ___, and _____

Back 21

muscle, liver, kidney

Front 22

in contrast to the liver and kidney, which catabolize glycogen during fasting and exercise to ___________, muscles simply utilize glycogen as energy during these times

Back 22

raise blood sugar levels

Front 23

gluconeogenesis cannot operate to any significant without _____, where the pyruvate to oxaloacetate conversion takes place

Back 23

mitochondria

Front 24

RBCs have no ___________, so they cannot utilize ________ or ________ for energy, nor can they carry out the __________ and ________ pathways; they can only use the ________ and __________ pathways

Back 24

have no mitochondria; cannot use fat or protein for energy; cannot carry out the TCA cycle or oxidative phos; can only use glycolysis and the PPP

Front 25

RBCs do not store _________ and therefore need a continual supply of _______

Back 25

glycogen, glucose

Front 26

the ______ is important to RBCs because they need reduced ________ to protect their membranes; in RBCs, the primary products of this pathway are NADPH and pyruvate

Back 26

PPP, reduced glutathione

Front 27

most of the pyruvate produced in RBCs is converted to _________ and transported out of the cell for ________

Back 27

lactate, hydroxyl ion exchange

Front 28

______ catalyzes the rxn:

pyruvate+NADH <==> lactate+ NAD+

Back 28

LDH

Front 29

tissues with few mitochondria are: 1) ______ 2) _________, 3) _______ 4) _______ ; these tissues require 40g/day of _______ and release _______ and _____ into the blood as end products of glucose metabolism

Back 29

kidney medulla, testis, leukocytes, white muscle fibers

Front 30

the brain metabolizes glucose via both _________ and __________; it has mitochondria and lots of O2, so it combusts ______ to _____ and H2O for maximal energy yield

Back 30

glycolysis, the PPP; combusts pyruvate ---> CO2 + H2O

Front 31

the brain does not normally use ____ as an energy source and does not store _____, so it depends on a constant supply of glucose (___ g/day); however, it can partially adapt to other energy sources (eg _________) during prolonged starvation

Back 31

does not use fat or store glycogen; needs 120g/day glucose; can use ketone bodies in a pinch

Front 32

adipose tissue metabolizes glucose by both ____________ and ______ pathways. Pentose phosphate is an important source of _____ for fat biosynthesis.

Back 32

glycolytic, pentose phosphate; NADPH

Front 33

adipose tissue has a ____________ to store and metabolize glycogen for its own use

Back 33

limited capacity

Front 34

in adipose tissue, most of the pyruvate from glycolysis is either ______ or _______

Back 34

used for energy production or converted to fat.

Front 35

_________ is not dependent on glucose; as blood insulin/glucose levels fall, it simply metabolizes fat

Back 35

adipose tissue

Front 36

the skeletal and heart muscle - metabolize glucose by both _____ and ________ pathways, but the ______ pathway normally predominates

Back 36

glycolytic and PPP; glycolytic

Front 37

the heart and skeletal muscle has a __________ capacity to store and metabolize glycogen for its own use

Back 37

significant

Front 38

________ can utilize the citric acid cycle and oxidative phosphorylation to derive energy from pyruvate and to oxidize fats for energy. Thus, _________ can easily switch to fat as an energy source as blood glucose levels and glycogen stores decrease.

Back 38

resting muscle, resting or lightly exercising muscle

Front 39

____________ are a major source of protein in extreme cases of need

Back 39

muscle

Front 40

in _________ the demand for energy exceeds the rate at which O2 can be transported to the muscle and/or substrates transported into the mitochondria. Thus, a readily available source of glucose is partially limiting for endurance or high output exercise. Under these conditions a significant fraction of the pyruvate will be converted to ______ or, if high levels of NH4+ are present, to ______ and exported into the blood.

Back 40

rapidly contracting muscle; lactate, alanine

Front 41

the liver and kidney metabolize glucose via both _______ and _________ pathways

Back 41

glycolytic and pentose phosphate

Front 42

in the liver and kidney, pentose phosphate is important for the production of NADPH for _________, _________, and ______. Also, the liver and kidney metabolize glucose by the ________ (detoxification).

Back 42

biosynthesis, production of reduced glutathione and microsomal enzyme systems; the glucuronic acid pathway

Front 43

the liver and kidney (do, do not) depend on glucose

Back 43

do NOT

Front 44

the liver and kidney (can, cannot) use fat as an energy source

Back 44

can

Front 45

the ______ and ________ can readily provide stored glycogen to raise blood glucose when needed

Back 45

liver and kidney

Front 46

glucose is stored as either _______ or ________

Back 46

glyocen, fat

Front 47

metabolically important glycogen stores are in _______, __________ and ________

Back 47

muscle, kidney, liver

Front 48

Most of the fat is produced & and stored in _________; some of the fat is also produced in the liver and is exported as _____ for eventual storage in the adipose tissue.

Back 48

the adipose tissue; lipoproteins

Front 49

As glycogen reserves start to become depleted, _________ becomes the major source of blood glucose.

Back 49

gluconeogenesis

Front 50

The major source of carbons for gluconeogenesis in the fasting state are _____ from the breakdown of protein stores in muscle. _____ can also be a source of carbons for gluconeogenesis

Back 50

amino acids, lactate

Front 51

For the human body, lactate production is _________.

Back 51

~115 g/day

Front 52

____ in the liver plays a major role in ridding the body of lactate, thus preventing a metabolic acidosis from the accumulation of lactate (remember glycolysis produces one proton for every molecule of lactate).

Back 52

GNG

Front 53

The continuous conversion of glucose to lactate by some tissues (via glycolysis) and the counterbalancing conversion of lactate to glucose by the liver (via gluconeogenesis) is referred to as the ________

Back 53

Cori Cycle

Front 54

The accumulation of lactate can drive _____ in the liver by mass action.

Back 54

gluconeogenesis

Front 55

Not all lactate needs to be converted back to glucose via gluconeogenesis. Lactate is a perfectly good energy source for any tissue that has ___, _______ and _____ .

Back 55

lactate dehydrogenase, mitochondria and a sufficient source of oxygen.

Front 56

Anaerobic exercise is characterized by extremely vigorous exercise of short duration (examples = sprinting and weight lifting). This type of exercise is primarily performed by _______ (also referred to as type II, glycolytic or white muscle).

Back 56

fast-twitch muscle fibers

Front 57

Fast-twitch muscle fibers have relatively few _______ and rely on ______ for most of their energy

Back 57

mitochondria, anaerobic glycolysis

Front 58

During anaerobic exercise, blood glucose can’t get into the muscle fast enough to make a major contribution to vigorous exercise, so the main sources of energy are _____, _______ and _______.

Back 58

ATP, phosphocreatine and muscle glycogen.

Front 59

aerobic/lower intensity exercise is primarily performed by ________ (also called type I, oxidative or red muscle).

Back 59

slow-twitch muscle fibers

Front 60

slow-twitch muscle fibers have abundant _____, so they can oxidize glucose all the way to CO2 and H2O and they can use fat as an energy source

Back 60

mitochondria

Front 61

during aerobic exercise, ___ and _____ make a significant contribution to energy needs (by maintaining blood glucose) with fat making an increasing contribution as glycogen stores are exhausted

Back 61

liver glycogen and the Cori cycle

Front 62

Fats can only supply ______ of VO2 max.

Back 62

50%

Front 63

carbs are consumed in the diet mainly as ________ and ______; these are hydrolyzed to _______ in the digestive tract

Back 63

polysaccharides and disaccharides; monosaccharides

Front 64

The monosaccharides released in the digestive process are absorbed into the mucosal cells and passed into circulation through the ________

Back 64

hepatic portal vein

Front 65

Since the major dietary polysaccharide,______, is composed entirely of glucose, glucose is the most abundant monosaccharide available to the cell

Back 65

starch

Front 66

________ and ________ are both converted to glucose in the ______

Back 66

fructose and galactose, liver

Front 67

Galactose 1-Phosphate Uridyl Transferase Deficiency (“Classic” Galactosemia) is a ______ hereditary disease

Back 67

recessive

Front 68

__________ across the plasma membranes of cells is the initial event in cellular glucose metabolism and is often the rate limiting step in metabolism

Back 68

facilitative glucose transport

Front 69

Glucose Transporters __ and ____ have low Kms for glucose and therefore responsible for basal levels of transport

Back 69

1 & 3

Front 70

_____ is the insulin-sensitive glucose transporter, found mostly in muscle and adipose tissue

Back 70

GLUT-4

Front 71

Insulin affects glucose transporter by causing _____ of a pool of transporters localized in intracellular vessicles to the plasma membrane; this occurs via IRS activation of the regulatory subunit (p85) of ________

Back 71

translocation; PI3 kinase

Front 72

In muscle ______ is also translocated to the plasma membrane in response to electrical stimulation of the muscle.

Back 72

GLUT-4

Front 73

________ is only found in cells that regulate glucose homeostasis, such as liver and pancreatic B-islet cells.

Back 73

GLUT-2

Front 74

the high Km of ______ causes glucose uptake to be proportional to the highest physiological glucose concentration and thus allows extracellular glucose concentration to govern the usage of glucose in in liver and B-islet cells of the pancreas; _____ extracellular glucose levels drive utilization of glucose (primarily conversion to glycogen and fat) in liver and the magnitude of the insulin response in B-islet cells.

Back 74

GLUT-2; high extracellular glucose levels

Front 75

Decreased expression and/or mutations of _____ are seen in some diabetics.

Back 75

GLUT-2

Front 76

Amino acids also stimulate insulin release by _________

Back 76

B-cells

Front 77

The enzyme ______ catalyzes phosphorylation of glucose. It has a Km for glucose of 0.1 mM which means that at the glucose concentrations prevailing in most cells it is saturated and is reacting at its maximal velocity

Back 77

hexokinase

Front 78

_________ is the rate limiting enzyme for glycolysis and is the principal control point in glycolysis.

Back 78

phosphofructokinase (PFK)

Front 79

PFK is an ______ enzyme that is inhibited by ATP and activated by AMP. This enzyme is, therefore, inhibited when the cell has high levels of ATP. The enzyme is also inhibited by ____, ________, _________ and ________.

Back 79

allosteric; low pH, NADH, citrate, and long chain fatty acids

Front 80

F-2,6-P2 binds to an allosteric site on PFK and ______ its affinity for fructose-6-phosphate and _______ its inhibition by ATP

Back 80

increases, decreases

Front 81

the enzyme ________ catalyzes the irreversible reaction (phosphoenol pyruvate + ADP ---> pyruvate + ATP) during glycolysis

Back 81

pyruvate kinase

Front 82

For glycolysis: In the first few steps, 2 ATP are used to produce fru-1,6-P2; however, there are 2 later steps where _________ of ADP to ATP occurs. Since this occurs for each of the 2 trioses derived from glucose, 4 ATP are synthesized. Therefore, the net ATP synthesized = ___. This is all the ATP that can be produced by anaerobic or amplified glycolysis.

Back 82

substrate level phosphorylation; 2

Front 83

in mammals, temporary anoxia results in _______ glycolysis

Back 83

increased

Front 84

"amplified glycolysis" occurs in: (3)

Back 84

1) muscle during vigorous exercise 2) cells that have continuously altered levels of PFK effectors such as many tumor cells 3) cells that are incapable of oxidative phosphorylation, such as erythrocytes.

Front 85

If we look at exercising muscle, ______ levels are high and both _____ & ______ levels are low.

Back 85

fructose-2,6-bisPi; ATP & citrate

Front 86

Under normal conditions the reducing equivalents present in NADH are transferred to the mitochondria where they can be used to generate ATP via ______. However, ______, so one of two shuttle systems must be used to get the reducing equivalents into the mitochondria- either the a) ________ (in all tissues) or the b) _____

Back 86

oxidative phosphorylation; NADH cannot cross the membrane directly; a) glycerol phosphate shuttle b) malate shuttle

Front 87

All of the reactions of the GPS system are reversible, so the direction of the reactions is driven by _____.

Back 87

mass action

Front 88

3 characteristics of the GPS:

Back 88

1) In most cells, it is the major shuttle for transferring electrons from cytosolic NADH into the mitochondria 2) It converts NADH into NAD in the cytosol so that glycolysis can continue. 3 It generates 2 ATP/cytosolic NADH.

Front 89

2 characteristics of the malate shuttle:

Back 89

1) The malate shuttle allows the production of 3 ATPs from every cytoplasmic NADH 2) It is primarily used in high energy tissues such as heart muscle, and for biosynthetic reactions in other tissues.

Front 90

under conditions of amplified glycolysis, ________ is very important, since it can recycle the NADH (that would tend to accumulate) back to NAD+.

Back 90

LDH

Front 91

The molecular action of hydrophilic hormones is ultimately to regulate the activities of cellular hormones, including (3):

Back 91

enzymes, TFs, cytoskeletal proteins

Front 92

Four generalized classes of cell-surface receptors for hydrophilic hormones:

Back 92

1) G-protein 2) Enzyme (eg receptor tyrosine kinases, the cytoplasmic domain of which phosphorylates target cells) 2) Cytokine (eg Jak kinases ---> Stat TFs) 4) Ion-channel (ie neurotransmitters)

Front 93

G-proteins are ______ that undergo a cycle in which they hydrolyze GTP and then exchange the resulting GDP for GTP

Back 93

GTPases

Front 94

Effector enzyme/protein: adenylate cyclase

Back 94

Second messenger: cAMP

Front 95

Effector enzyme/protein: guanylate cyclase

Back 95

Second messenger: cAMP

Front 96

Effector enzyme/protein: phospholipase C

Back 96

Second messenger: (phosphotidylinosital system): diacylglycerol (DAG), inositol 1,4,5 triphospate (IP3)

Front 97

Effector enzyme/protein: Phosphatidylinositol-3-kinase

Back 97

Second messenger: Phosphatidylinositol-3,4,5 P (PIP3)

Front 98

Effector enzyme/protein: ion channel

Back 98

Second messenger: calcium

Front 99

protein kinases ___________ ; there are three kinds:

Back 99

transfer the gamma-PO4 from ATP to the hydroxyl group of serine, threonine, or tyrosine residues of proteins; 1) Ser/Thr 2) Tyr 3) dual

Front 100

protein phosphotases __________

Back 100

reverse the action of protein kinases by hydrolyzing phospho-serine, phospho-threonine, or phospho-tyrosine residues and restoring the side chains to the free hydroxyl form

Front 101

conserved structural feature of protein kinase catalytic domains (4): (hint-- ATP binding region is where? substrate? what's in between?)

Back 101

1) ATP binding lobe = small N-terminal lobe; 2) substrate binding lobe = large C-terminal lobe 3) catalytic center = cleft btw large and small lobes; 4) activation loop

Front 102

two major biochemical mechanisms for molecular relays:

Back 102

1) covalent phosphorylation of the target protein by protein kinases 2) exchange of GDP for GTP by G-proteins

Front 103

polypeptide hormones are formed from _________, which are:

Back 103

pre-pro-hormones; -encoded by genes -transcribed into mRNA
-translated into pre-pro-hormones
-processed to give the secreted and active form

Front 104

pre-pro-hormones are targeted to the __________. steps are:

Back 104

secretory pathway; 1) N-terminal signal peptide targets hormone precursors to the rough endoplasmic reticulum (ER)
2) Uptake into the ER lumen occurs during translation 3) Precursors progress through the Golgi network and are delivered to the plasma membrane in secretory vesicles 4) Processing to mature forms begins during these transitions.

Front 105

Pro-hormone converting enzymes (PCs) are ________ that cleave on the _______ side of the _____ amino acid sites; their processing begins in the __________ and may continue in the secretory vesicles

Back 105

serine proteases, carboxyl side, dibasic amino acid sites; trans-Golgi network

Front 106

POMC is synthesized in specialized _______, _________-, _______ in humans. It is a single gene that encodes multiple hormones.

Back 106

pituitary, brain, and skin cells

Front 107

Insulin processing steps:

Back 107

1) signal processing directs pre-pro-insulin to ER 2) conversion to pro-insulin occurs in the ER 3) pro-insulin transits through the Golgi to secretory vessicles 4) C-peptide is removed in secretory vessicles 5) targets: liver --> inhibit glucose production; muscle/adipose --->stimulate glucose uptake and use

Front 108

pleomorphic phenotypes result from (2)

Back 108

mutations in a single gene encoding more than one mature hormone OR prohormone processing enzymes

Front 109

Gs

Back 109

stimulates adenylate cyclase

Front 110

Gi

Back 110

inhibits adenylate cyclase

Front 111

Gq

Back 111

stimulates phospholipase Cbeta

Front 112

G12

Back 112

stimulates ion channels

Front 113

G-protein-GTP (active) =

Back 113

Kd-GDP

Front 114

G-protein-GDP (inactive) =

Back 114

kcat-GTP

Front 115

2nd messengers generally act by ____________

Back 115

reversing negative inhibition of key protein kinases

Front 116

all eight isozymes of adenylate cyclase are integral membrane proteins with _____ transmembrane domains

Back 116

12

Front 117

adenylate cyclase synthesizes ___ from ______

Back 117

cAMP from ATP

Front 118

PKA (protein kinase A) has 2 ______ and 2 _________ subunits and is found as an _________ in the absence of ______

Back 118

catalytic; negative regulatory; inactive holoenzyme (membrane-bound) in the absence of cAMP

Front 119

Upon the binding of cAMP, the ______ domains of PKA dissociate and _____ target proteins to modify their activity

Back 119

catalytic, phosphorylate

Front 120

GTP-Galphaq binding to phospholipase Cbeta (PLC) _______ its activity; PLC in turn catalyzes the synthesis of two second messengers, _____ and ______

Back 120

stimulates; diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3)

Front 121

____ (released by PLC via Gq stim) is a short lived 2nd messenger that induces the release of stored ____ from the ER by binding to a ___ channel in the ER membrane.

Back 121

IP3; Ca2+, Ca2+

Front 122

______ and ______ (hint: PLC, Gq path) reverse the negative regulation on protein kinase C (PKC) through their binding to the negative regulatory domain

Back 122

DAG and Ca2+

Front 123

Gi inhibits the _______ and stimulates the ________ signaling pathways (bc the free gamma-beta subunit stimulates PLC and activates the Pi-cycle PKC pathway)

Back 123

adenylate cyclase, phospholipase C

Front 124

4 structural characteristics shared by all G-protein coupled receptors:

Back 124

1) extracellular N-terminal domain 2) seven transmembrane-spanning a-helices 3) three extra and three intra cellular loops to connect helices 4) intracellular C-terminal domain

Front 125

_____ is the target of cholera toxin The A subunit of cholera toxin has ______ activity; ADP ribosylation of Arg201 strongly inhibits the GTPase activity of ___ and effectively traps it in the _____ state. This in turn causes prolonged activation of ______ resulting in elevated ______, which causes intestinal epithelial cells to secrete chloride and water into the lumen of the intestine resulting in rapid dehydration.

Back 125

Gs; ADP-ribosylating; Gs; activated; adenylate cyclase, cAMP

Front 126

___ is the target of pertussis toxin, the A subunit of which has ________ activity; this in turn ADP inhibits the _____, locking the GPCR in the inactive state; this, Gi cannot inhibit ________ activity and cAMP levels are elevated.

Back 126

Gi; ADP-ribosylating; exchange of GDP for GTP; adenylate cyclase

Front 127

The systemic efffects of pertussis toxin, which include increased insulin production (hypoglycemia) and increased sensitivity to histamine (increased capillary permeability, hypotension and shock), result in the toxin's ability to alter normal __ activity.

Back 127

Gi

Front 128

Hallmarks of testotoxicosis:

Back 128

1) post-puberty levels of testosterone and sex hormone binding protein by age 4; 2) normal pre-puberty levels of LH and gnRH; 3) testosterone secretion levels independent of normal regulation

Front 129

FPP is linked to a constitutively activating mutation of the ______ ; the disorder is inherited as a ________ trait.

Back 129

luteinizing hormone receptor; sex-limited autosomal dominant

Front 130

In FPP, the mutated receptor expressed in tissue culture cells stimulates ___ production in the absence of ___

Back 130

cAMP, LH

Front 131

Albright Hereditary Osteopathy, AHO, involves a deficiency in _____ that makes cells resistant to the action of hormones that signal through ___ coupled GPCRs.

Back 131

G-alpha-s; Gs

Front 132

AHO presents with ________

Back 132

resistance to parathyroid hormone

Front 133

Actions of PTH: 1) bone ---> (2) 2) kidney ---> (3); resistance causes _______

Back 133

bone: remodeling, release of Ca2+; kidney: Ca2+ clearance, phosphate clearance, vitamin D production; resistance causes hypocalcemia and hyperphosphatemia

Front 134

The first committed step for glycolysis is at ______; therefore, this is the primary regulation point. the second regulation point is the ______ rxn

Back 134

PFK; pyruvate kinase

Front 135

ATP inhibits ______ and stimulates _________

Back 135

PFK, FBP

Front 136

the Pasteur effect describes the inhibition of _______ by O2, because in the presence of O2, ____ levels are high

Back 136

glycolysis, ATP

Front 137

citrate inhibits _____ and stimulates ________

Back 137

PFK, FBP

Front 138

In the liver, the activity of PFK-2/FBP-2 is controlled by phosphorylation/dephosphorylation of the N-terminal regulatory region in response to the hormones _______ and ______. This serves as an override mechanism that controls glycolysis/gluconeogenesis in response to the whole body's need for blood glucose.

Back 138

glucagon and insulin

Front 139

F-2,6 bisP ______ PFK; F-2,6 bisP ______ FBP

Back 139

activates, inhibits

Front 140

In liver, glucagon & epinephrine result in a/an _______ in F-2,6 bisP levels

Back 140

DECREASE

Front 141

epi and glucagon activate _____; insulin activates ____

Back 141

PKA, receptor tyrosine kinase

Front 142

in the liver, insulin results in a/an ______ in F-2,6 bisP levels; in muscle, insulin has little to no effect

Back 142

increase

Front 143

defects in the __________ have recently been liked to Rapid-Onset Dystonia Parkinsonism and Familial Hemiplegic Migraine type 2

Back 143

Na+ - K+ ATPase pump

Front 144

asymmetry in Na/K pump:

Back 144

3 Na+ out; 2 K+ in

Front 145

Cholestatic conditions result from mutations in several different ____ in the biliary tree.

Back 145

ABCs

Front 146

Excitatory acetylcholine, glutamate and serotonin bind their receptors to _________ and depolarize while GABA (gamma-aminobutyric acid) and glycine _________ to attenuate depolarization by allowing Cl- entry or K+ exit down their concentration gradients.

Back 146

activate Na+ currents; activate Cl- or K+ channels

Front 147

Myasthenia Gravis is an autoimmune disease in which binding of antibodies to the receptor causes its ________ and loss of neuromuscular transmission.

Back 147

internalization and degradation

Front 148

inner mitochondrial membrane is particularly impermeable to molecules due to the high proportion of _______in the membrane.

Back 148

cardiolipin

Front 149

cytochrome c is located in the ______ of the mitochondria

Back 149

intermembrane space

Front 150

in oxidative phosphorylation, the transfer of electrons along the electron transport chain is coupled to the movement of protons (H+) from the_____ to the ______

Back 150

matrix side, inter membrane space

Front 151

arsenic

Back 151

Inhibits the pyruvate degydrogenase complex; prevents the generation of acetyl CoA.

Front 152

cyanide

Back 152

Inhibits complex IV of the ETC. Prevents the transport of electrons from cytochrome c oxidase to oxygen.

Front 153

rotenone

Back 153

Inhibits complex I of the ETC. Prevents the transfer of electrons from complex I to ubiquinone.

Front 154

Mitochondrial Uncouplers (2,4-dinitrophenol, DNP; FCCP):

Back 154

proton ionophors; can bind to protons and cross the mitochondrial inner membrane- thus dissipating the proton gradient.

Front 155

oligomycin

Back 155

Inhibits ATP Synthase (F1F0 ATPase), thus blocking ATP generation via oxidative phosphorylation.

Front 156

uncoupling proteins

Back 156

generate heat

Front 157

Charcot-Marie-Tooth 2A (CMT2A) disease is an axonopathy associated with mutations in the MFN2 genes that regulates ______.

Back 157

mitochondrial fusion

Front 158

________ is a large enzyme complex in the mitochondrion consisting of 3 different types of enzyme subunits. It is the enzyme that connects the glycolytic pathway to the citric acid cycle.

Back 158

pyruvate dehydrogenase

Front 159

dietary source/ coonzyme:

1) thiamine or vitamin B1

2) pantothenic acid

3) riboflavin

4) niacin

Back 159

1) thiamine pyrophosphate (TPP)

2) - coenzyme A (CoASH)

3) – FADH2

4) - NADH

Front 160

catalyzes a 2 step reaction )the first in the CAC): an aldol condensation of oxaloacetate and acetyl CoA, followed by hydrolysis to yield citrate and free CoA. The hydrolysis step is not easily reversible.

Back 160

citrate synthase

Front 161

second major CAC enzyme; a multi-enzyme complex very similar to pyruvate dehydrogenase. This step is irreversible. It also produces NADH.

Back 161

alpha-ketoglutarate dehydrogenase

Front 162

third major CAC enzyme; has a high negative detaG°' of hydrolysis, and can, therefore, be coupled to the direct phosphorylation of GDP to GTP (which is equivalent to ATP); this reaction is fairly reversible. This is an example of substrate level phosphorylation.

Back 162

succinyl CoA synthetase

Front 163

final major enzyme of CAC; this is a good example of a reaction that has a net flow opposite to an unfavorable Keq. That is the oxidation of malate by NAD+ to produce oxaloacetate + NADH + H+ has a ∆G°' of + 7 kcal/mole.

Back 163

malate dehydrogenase

Front 164

breakdown of net ATP generated by glycolysis + CAC:

Back 164

6 in cytosol, 30 in mitochondria

Front 165

the CAC is tightly regulated by oxygen supply via ___ inhibition (which is produced by oxidative phosphorylation)

Back 165

NADH

Front 166

_____ stimulates the citric acid cycle at several points. This is important because electrical stimulation of the muscle causes an increase in intracellular ____ levels. Thus, the CAC is maximally stimulated in muscles.

Back 166

Ca2+

Front 167

________ is a required cofactor for the transaminase reactions in the CAC. It comes from vitamin B6 in the diet.

Back 167

Pyridoxal Phosphate

Front 168

net conversion of ______ to carbohydrate and most amino acids is not possible

Back 168

fatty acids

Front 169

the citric acid cycle requires a constant supply of ________ to keep going

Back 169

oxaloacetate

Front 170

dyslipidimia is an early indicator of ______

Back 170

type II diabetes

Front 171

C-reactive protein, which increases during DMtII, is a predictor of ____

Back 171

heart disease

Front 172

b) Thiazolidinedione (Actos & Avandia) drugs are _____ of PPAR-gamma (which controls adipocyte differentiation) and are used to improve insulin sensitivity in insulin resistant patients. Examples are Actos and Avandia

Back 172

agonists

Front 173

______ (eg TNFalpha and free fatty acids) are thought to modulate insulin resistance to DMtII

Back 173

adipokines

Front 174

complications of diabetes:

Back 174

muscle degradation, cataracts (aldol reductase, sorbitol), non-enzymatic glycosylation of proteins (HbA1c),

Front 175

the PPP is driven entirely by _____; it provides _____ for nucleic acids and _____ for biosynthesis and detoxification reactions

Back 175

mass action; pentoses; NADH

Front 176

NADPH produced by the oxidative portion of the PPP is used for (3):

Back 176

for biosynthetic reactions (eg. fatty acid biosynthesis), for reduction of glutathione, and for reduction of ribose to deoxyribose

Front 177

the non-oxidative portion of the PPP provides (2); ______ is a required cofactor

Back 177

ribose-5-phosphate for nucleotide synthesis and cytoplasmic NADPH; Thiamine pyrophosphate is an essential cofactor

Front 178

a rapidly dividing cell would most likely utilize the _____ of the PPP; a cell that needs both NADPH and r5p in balance (liver, kidney) would use the ____ portion; cells that need more NADPH than r5p (RBCs) would use _______ of the pathway

Back 178

non-oxidative (for the ribose-5-phosphate); oxidative; both

Front 179

defects in ________ result in individuals being unable to produce NADPH via the PPP, which causes rare complications with RBCs under circumstances of high ROS levels (ie treatment with some antimalarials)

Back 179

glucose 6-phosphate dehydrogenase

Front 180

symptoms of ________, an autosomal ______ deficiency of glucose 6-phosphatase in the liver (5):

Back 180

Von Gierke’s Disease, recessive; 1) hetapomegaly due to lots of glycogen 2) fasting hypoglycemia 3) lactic acidemia 4) hyperlipidemia 5) hyperuricemia

Front 181

_________ occurs when one drug indirectly decreases the amount of a second drug that
would otherwise be available to its site of action. Many agents such as phenobarbital, induce the microsomal enzyme activity responsible for the biotransformation of other drugs.

Back 181

biochemical antagonism

Front 182

Certain Safety Factor: CSF =

Back 182

LD1/ED99

Front 183

Bioavailability, (F) =

Back 183

(AUCoral)/(AUCi.v.) x (Dosei.v.)/(Doseoral)

Front 184

ion trapping

Back 184

more (ionized) drug is found on the side of the membrane where ionization occurs to the greatest extent