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Flashcards in biochem: metabolism Deck (172):
1

kinase

used ATP to add a (high E) phosphate group

2

phosphorylase

adds inorganic phosphate w/o ATP

3

phosphatase

removes phosphate group

4

dehydrogenase

catalyzes redox rxns

5

hydroxylase

adds -OH

6

carboxylase

transfers CO2 groups w/help from biotin

7

mutase

relocates a fxnal group w/in a molecule

8

mitochondrial metabolism

fatty acid oxidation (beta-oxidation), acetyl-CoA production, TCA cycle, oxidative phosphorylation, ketogenesis

9

cytoplasmic metabolism

glycolysis, fatty acid synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER), cholesterol synthesis

10

mitochondrial AND cytoplasmic metabolism

HUGS take two: Heme synthesis, Urea cycle, Gluconeogenesis

11

glycolysis rate-limiting enzyme

PFK-1

12

glycolysis regulators

+: AMP, fructose-2,6-bisphosphate. -: ATP, citrate

13

gluconeogenesis rate-limiting enzyme

fructose-1,6-bisphosphatase

14

gluconeogenesis regulators

+: ATP, acetyl-CoA. -: AMP, fructose-2.6-bisphosphate

15

TCA cycle rate-limiting enzyme

isocitrate dehydrogenase

16

TCA cycle regulators

+: ADP. -: ATP, NADH

17

glycogenesis rate-limiting enzyme

flycogen synthase

18

glycogenesis regulators

+: G6P, insulin, cortisol. -: epinephrine, glucagon

19

glycogenolysis rate-limiting enzyme

glycogen phosphorylase

20

glycogenolysis regulators

+: epinephrine, glucagon, AMP. -: G6P, insulin, ATP

21

HMP shunt rate-limiting enzyme

G6PD

22

HMP shunt regulators

+:NADP+. -: NADPH

23

de novo pyrimidine rate-limiting enzyme

carbamoyl phosphate synthetase II

24

de novo pyrimidine regulators

+: ATP. -: UTP

25

de novo purine synthesis rate-limiting enzyme

PRPP amidotransferase

26

de novo purine synthesis regulators

-: AMP, inosine monophosphate (IMP), GMP

27

urea cycle rate-limiting enzyme

carbamoyl phosphate synthetase I

28

urea cycle regulators

+: N-acetylglutamate

29

fatty acid synthesis rate-limiting enzyme

acetyl-CoA carboxylase (ACC)

30

fatty acid synthesis regulators

+: insulin, citrate. -: glucagon, palmitoyl-CoA

31

fatty acid oxidation rate-limiting enzyme

carnitine acyltransferase I

32

fatty acid oxidation regulators

-: malonyl-CoA

33

ketogenesis rate-limiting enzyme

HMG-CoA synthase

34

cholesterol synthesis rate-limiting enzyme

HMG-CoA reductase

35

cholesterol synthesis regulators

+: insulin, thyroxine. -: glucagon, cholesterol

36

aerobic glucose metabolism

net + 32 ATP via malate-aspartate shuttle (heart and liver), 30 net ATP via glycerol-3-phosphate shuttle (muscle)

37

anaerobic glycolysis

net + 2 ATP/glucose

38

arsenic

causes glycolysis to produce 0 net ATP. inhibits lipoic acid. -> vomiting, rice-water stools, garlic breath

39

activated ATP carries

phosphoryl groups

40

activated NADH, NADPH, FADH2 carry

electrons

41

activated CoA, lipoamide carry

acyl groups

42

activated biotin carries

CO2

43

activated tetrahydrofolates carry

1-C units

44

activated S-adenosylmethionine (SAM) carries

CH3 groups

45

activated TPP carries

aldehydes

46

NADPH

= product of HMP shunt. used in: anabolic processes, respiratory burst, cytochrome P-450 system, glutathione reductase

47

universal electron acceptors

NAD+ (from vit B3), NADP+, FAD+ (from vit B2)

48

NAD+ vs. NADPH

NAD+: generally catabolic, carries reducing equivalents away. NADPH: generally anabolic (e.g. steroid and fatty acid synthesis), supplies reducing equivalents

49

hexokinase

in most tissues except liver and pancreatic beta cells. low Km (high affinity), low Vmax (low capacity), not induced by insulin. + feedback inhibition by G6P.

50

glucokinase

in liver, pancreas beta cells. high Km (low affinity), high Vmax (high capacity), induced by insulin. no feedback inhibition by G6P. gene mutation associated w/maturity-onset diabetes of the young

51

hexokinase vs. glucokinase

both can phosphorylate glucose into G6P: 1st step of glycolysis or glycogen synthesis. low [glu], hexokinase sequesters it in tissues. high [glu], liver stores it

52

FBPase-2 and PFK-2 in fasting state

inc. glucagon -> inc. cAMP -> inc. PKA -> inc. FBPase-2, dec. PFK-2, less glycolysis, more gluconeogenesis

53

FBPase-2 and PFK-2 in fed state

inc. insulin -> dec. cAMP -> dec. PKA -> dec. FBPase-2, inc. PFK-2, more glycolysis, less gluconeogenesis

54

pyruvate dehydrogenase complex

mitochondrial enzyme complex linking glycolysis and TCA cycle. active in fed state. similar to alpha-detoglutarate dehydrogenase complex in TCA cycle. 3 enzymes, 5 cofactors: pyrophosphate, FAD, NAD, CoA, and lipoic acid. exercise -> inc. NAD+/NADH ratio, inc. ADP, inc. Ca 2+ -> activation of complex.

55

pyruvate dehydrogenase complex deficiency

causes buildup of pyruvate that gets shunted to lactate via LDH and alanine via ALT. X-linked

56

pyruvate dehydrogenase complex deficiency: findings

neurologic defects, lactic acidosis, inc. serum alanine. starts in infancy

57

pyruvate dehydrogenase complex deficiency: Tx

inc. intake of ketogenic nutrients (high fat, high lysine and leucine). Lysine and Leucine - the onLy pureLy ketogenic AAs.

58

4 possible products of pyruvate

alanine, oxaloacetate, acetyl-CoA, lactate

59

pyruvate -> alanine

via alanine aminotransferase (ALT) w/B6. alanine carries amino groups to liver from muscle. in cytosol

60

pyruvate -> oxaloacetate

via pyruvate carboxylase (PC) w/biotin. oxaloacetate can replinish TCA cycle of be used in gluconeogenesis. requires CO2 and ATP. in mitochondria

61

pyruvate -> acetyl-CoA

via pyruvate dehydrogenase (PDH) w/B1, B2, B3, B5, lipoic acid. transition from glycolysis to TCA cycle. NAD+ in, NADH, H+, and CO2 out. occurs in mitochondria.

62

pyruvate -> lactate

= cori cycle. via LDH w/B3. end of anaerobic glycolysis, the major pathway in RBCs, WBCs, kidney medulla, lens, testes, and cornea.

63

krebs cycle mnemonic

Citrate Is Krebs' Starting Substrate For Making Oxaloacetate: Citrate, Isocitrate, alpha-Ketoglutarate, Succinyl-CoA, Succinate, Fumarate, Malate, Oxaloacetate

64

TCA cycle produces

3 NADH, 1 FADH2, 2CO2, 1 GTP per acetyl-CoA = 10ATP/acetylCoA (2x/glucose).

65

e- transport chain: ox phos

NADH electrons from glycolysis enter mitochondria via shuttles to complex I. FADH2 electrons are transferred to complex II (lower E than NADH). electron transport creates a proton gradient that is coupled w/ox phos to drive ATP production

66

NADH -> _ATP

2.5ATP

67

FADH2 -> _ATP

1.5ATP

68

electron transport inhibitor poisons

rotenone, cyanide, antimycin A, CO. directly inhibit electron transport, causing a dec. proton gradient and block of ATP synthesis

69

ATP synthase inhibitor poisons

oligomysin. directly inhibit mitochondrial ATP synthase, causing an inc. proton gradient. no ATP is produced b/c electron transport stops

70

uncoupling agent poisons

2,4-dinitrophenol (illicit wt. loss drug), aspirin (OD -> fever), thermogenin in brown fat. inc. permeability of membrane causes dec. proton gradient and inc. O2 consumption. ATP synthesis stops, but electron transport continues. produces heat.

71

irreversible enzymes in gluconeogensis

Pathway Produces Fresh Glucose: Pyruvate carboxylase, Phosphoenolpyruvate, Fructose-1,6-bisphosphatase, Glucose-6-phosphatase.

72

pyruvate carboxylase

in mitochondria. pyruvate -> oxaloacetate. requires biotin, ATP. activated by acetyl-CoA

73

phosphoenolpyruvate carboxykinase

in cytosol. oxaloacetate -> phosphoenolpyruvate. requires GTP

74

fructose-1,6-bisphosphatase

in cytosol. fructose-1,6-bisphosphate -> fructose-6-phosphate. +: citrate. -: 2,6-bisphosphate

75

glucose-6-phosphatase

in ER. G6P -> glucose

76

gluconeogenesis

occurs primarily in liver. maintains euglycemia during fasting. enzymes are also in kidney, intestinal epithelium. enzyme deficiency -> hypoglycemia. muscle can't do it b/c it has no G6Pase. only odd-chain fatty acids can participate, even chains can't b/c they yield acetyl-CoA instead of propionyl-CoA, which enters as succinyl-CoA

77

HMP shunt

provides NADPH from G6P. also makes ribose for NA synthesis and glycolytic intermediates. 2 phases: oxidative and non-oxidative. both occur in cytoplasm in lactating mammary glands, liver, adrenal cortex, RBCs. no ATP is used or made.

78

oxidative phase of HMP shunt

G6P dehydrogenase converts G6P -> ribulose-5-P, yielding CO2 and 2 NADPH. rate-limiting step. irreversible

79

nonoxidative phase of HMP shunt

phosphopentose isomerase and transketolases convert ribulose-5-P -> ribose-5-P, G3P and fructose-6-P. reversible. requires B1

80

G6P dehydrogenase deficiency

can't make NADPH, so can't keep glutathione reduced, so free radicals accumulate. In RBCs, this causes hemolytic anemia, worsened by fava beans, sufas, primaquine, TB drugs, infection, inflammation. X-linked recessive. most common in AAs - inc. malarial resistance. will see heintz bodies and bite cells

81

essential fructosuria

defective fructokinase. autosomal recessive. benign, asymptomatic. fructose d/os are milder than analagous galactose d/os

82

fructose intolerance

autosomal recessive aldolase B deficiency. fructose-1-P accumulates in cells -> dec. available phosphate -> inhibition of hlycogenolysis and gluconeogenesis. Sx present after consuming fruit, juice, or honey. Udip = neg but regucing sugar can be detected in urine. Sx: hypoglycemia, jaundice, cirrhosis, vomiting. Tx: avoid fructose and sucrose

83

galactokinase deficiency

autosomal recessive. galactitol accumulates if galactose is consumed in diet. relatively mild. Sx: galactose in blood and urine, infantile cataracts, which can present as failure of social smile or object tracking

84

classic galactosemia

autosomal recessive absence of galactose-1-phosphate uridyltransferase. toxic falactitol and other substances accumulate. Sx: FTT, jaundice, hepatomegaly, infantile cataracts, intellectual disability, E coli sepsis (commonly fatal). Tx: exclude falactose and lactose from diet. also causes phosphate depletion.

85

fructose/galactose mnemonic

FAB GUT: Fructose is to Aldolase B as Galactose is to UridylTransferase

86

sorbitol

= glucose's alcohol counterpart. conversion via aldose reductase traps it inside the cell. some tissues (liver, ovaries, seminal vesicles) convert sorbitol -> fructose via sorbitol dehydrogenase. other tissues (schwann cells, retina, kidneys, lens) are at risk of accumulating sorbitol -> osmotic damage: cataracts, retinopathy, peripheral neuropathy, as seen w/chronic hyperglycemia in DM.

87

types of lactase deficiency

primary: common. age-dependent decline after childhood 2/2 absense of lactase-persistent allele.
secondary: los of BB 2/2 gastroenteritis (e.g. rotavirus), autoimmune dz, etc.
congenital: rare, due to defective gene

88

lactase deficiency

Dx: stool: low pH. breath: high hydrogen content following lactose tolerance test. intestinal Bx: normal (if congenital)
Sx: bloating, cramps, flatulence, osmotic diarrhea.
Tx: avoid dairy or take lactase pills

89

essential AAs

need to be consumed in the diet.
glucogenic: methionine, valine, histidine
glucogenic/ketogenic: isoleucine, phenylalanine, threonine, tryptophan
ketogenic: leucine and lysine

90

acidic AAs

aspartic acid, glutamic acid. negatively charged at normal pH

91

basic AAs

arginine (most basic), lysine, histidine (no charge at normal pH). Arg and His are required during periods of growth. Arg and Lys are used by histones to bind - charged DNA

92

urea cycle mnemonic

Ordinarily, Careless Crappers Are Also Frivolous About Urination: Ornithine, Citrulline, Aspartate, Argininosuccinate, Fumarate, Arginine, Urea

93

urea cycle

AA catabolism -> formation of common metabolites (e.g. pyruvate, acetyl-CoA), which serve as fuels. this process generates excess NH3, which is converted to urea and excreted renally. substrates: NH3, CO2, ATP. products: urea, AMP, fumarate. takes place in the liver

94

cahill cycle

alanine transports ammonia from muscle -> liver. alanine is converted to glucose to complete cycle.

95

cori cycle

lactate (in muscle) -> lactate (in liver) -> pyruvate -> glucose (liver -> muscle) -> pyruvate -> lactate

96

ammonia is carried by

glutamate (w/in cells) and alanine

97

hyperammonemia

can be acquired (e.g. liver dz) or hereditary (e.g. urea cycle defects). -> excess NH4+, which depletes alpha-ketoglutarate, inhibiting the TCA cycle. Tx: limit protein intake. lactulose: acidified GI tract, trapping ammonia for excretion. rifampin: dec. colonic ammoniagenic bacteria. benzoate/phenylbutyrate: bind AAs -> excretion

98

ammonia intoxication

tremor (asterixis), speech slurring, somnolence, vomiting, cerebral edema, vision blurring

99

N-acetylglutamate synthase deficiency

required cofactor for carbamoyl phosphate synthetase I. absense -> hyperammonemia. presents in neonates as poorly regulated respiration and body T, poor feeding, dev. delay, intellectual disability. identical presentation to carbamoyl phosphate synthetase I deficiency

100

ornithine transcarbamylase deficiency

X-linked (other urea cycle defects are autosomal recessive). most common urea cycle d/o. interferes w/ammonia excretion. often presents in 1st few days of life but can be later. excess carbamoyl phosphate -> orotic acid.
findings: inc. orotic acid in blood and urine, dec. BUN, Sx of hyperammonemia. NO megaloblastic anemia (vs. orotic aciduria).

101

phenylalanine derivatives

tyrosine, thyroxine, melanin, dopamine, NE, epi

102

tryptophan derivatives

niacin, 5HT, melatonin

103

histidine derivative

histamine

104

glycine derivatives

porphyrin, heme

105

glutamate derivatives

GABA, glutathione

106

arginine derivatives

creatine, urea, NO

107

deficient enzyme in PKU

phenylalanine hydroxylase (phenylalanine -> tyrosine)

108

deficient enzyme in albinism

tyrosinase (DOPA (dihydroxyphenylalanine) -> melanin)

109

deficient enzyme in alkaptonuria

homogentisate oxidase (homogentisic acid -> maleylacetoacetic acid - part of tyrosine --> fumarate -> TCA cycle)

110

phenylketonuria

autosomal recessive. tyrosine becomes essential. if due to missing tetrahydrobiopterin cofacter, called malignant PKU. findings: intellectual disability, growth retardation, seizures, fair skin, eczema, musty odor. Tx: dec. phenylalanine (aspartame) and inc. tyrosine in diet. supplement tetrahydrobiopterin. Aromatic AA -> odor! screening 2-3 days after birth (normal levels at birth)

111

maternal PKU

lack of proper dietary therapy during pregnancy -> microcephaly, intellectual disability, growth retardation and congenital heart defects in baby

112

maple syrup urine dz mnemonic

I Love Vermont maple syrup (trees have branches): blocked degradation of branches AAs Isoleucine, Leucine, and Valine

113

maple syrup urine dz

dec. alpha-detoacid dehydrogenase (B1) -> inc. alpha-ketoacids in blood (esp. of leucine) -> severe CNS defects, intellectual disability, death. Tx: restrict isoleucine, leucine, and valine in diet, supplement thiamine

114

alkaptonuria

= ochronosis. autosomal recessive deficiency of homogentisate oxidase -> tissue accumulation of pigment-forming homogentisic acid. usually benign. findings: dark connective tissue, brown pigmented sclerae, urine turns black when exposed to air. can cause debilitating arthralgia b/c homogentisic acid = toxic to cartilage

115

homocystinuria types

3 types, all autosomal recessive:
cystathionine synthase deficinecy (Tx: dec. methionine, inc. cysteine, B12, and folate in diet)
dec. affinity of cystathionine synthase or pyridoxal phosphate (Tx: inc. B6 (lots) and cysteine in diet)
homocysteine methyltransferase (methionine synthase) deficiency (Tx: inc. methionine in diet)

116

homocystinuria

-> excess homocysteine. findings: lots of homocysteine in urine, intellectual disability, osteoporosis, marganoid habitus, kyphosis, downward lens subluxation, thrombosis, atherosclerosis (stroke, MI)

117

cystinuria

autosomal recessive, common defect of renal PCT and intestinal AA transporter that prevents reabsorption of COLA: Cysteine, Ornithine, Lysine, Arginine. excess urine cystine -> recurrent hexagonal kidney stones. Tx: urinary alkalinization (potassium citrate, acetazolamine), chelating agents (e.g. penicillamine) -> inc. solubility. good hydration. Dx: urinary cyanide-nitroprusside test

118

cystine

2 cysteines connected by disulfide bond

119

glycogen regulation by insulin

insulin binds tyrosine kinase dimer receptor in liver and muslce -> + glycogen synthase (glucose -> glycogen) and protein phosphatase (+ glycogen synthase, - glycogen phosphorylase). net: more glycogen

120

glycogen regulation by glucagon

glucagon binds receptor in liver -> +cAMP -> +PKA -> + glucogen phosphorylase kinase -> glycogen phosphorylase (glucogen -> glucose). net: less glycogen, more glucose available

121

glycogen regulation by epinephrine

binds beta receptor in liver and muscle -> +cAMP -> +PKA -> + glucogen phosphorylase kinase -> glycogen phosphorylase (glucogen -> glucose).
binds alpha receptor in liver -> ER releases Ca -> + glycogen phosphorylase kinase and +Ca-calmodulin in contracting muscle -> + glycogen phosphorylase kinase
net: less glycogen, more glucose available

122

glycogen bonds

branches: alpha-(1,6) bonds. linkages: alpha-(1,4) bonds

123

glycogen in skeletal muscle

glycogenolysis -> G1P -> G6P -> fuel

124

glycogen in hepatocytes

stored. glycogenolysis to maintain normal blood sugar. glycogen phosphorylase frees G1Ps until 4 glucose per branch, then 4-alpha-D-glucanotransferase (debranching enzyme) moves 3 G1Ps from the branch to the linkage. then alpha-1,6-glucosidase (debranching enzyme) cleaves the last glucose - everything is free!

125

limit dextrin

the 1-4 glucose residues that remain on a branch after glycogen phosphorylase has shortened it

126

glycogen storage dzs

12 types, all causing glycogen accumulation in cells. Very Poor Carbohydrate Metabolism: Con gierke dz (type I), Pompe dz (type II), Cori dz (type III), McArdle dz (type V)

127

von gierke dz

autosomal recessive. Sx: severe fasting hypoglycemia, inc. glycogen in liver, blood lactate, triglycerides, uric acid, and hepatomegaly. Tx: frequent oral glucose/cornstarch, avoid fluctose and galactose. deficient enzyme: G6Pase

128

pompe dz

autosomal recessive. Pompe trashes the Pump (heart, liver, muscle). Sx: cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, early death. deficient enzyme: lysosomal alpha-1,4-glucosidase (acid maltase)

129

cori dz

autosomal recessive. gluconeogenesis = intact. Sx: milder type I w/normal blood lactate levels. deficient enzyme: alpha-1,6-glucosidase (debranching enzyme)

130

mcardle dz

autosomal recessive. Mcardle = Muscle. normal blood glucose. Sx: inc. glycogen in muscle (which can't break it down) -> painful muscle cramps, myoglobinuria w/strenuous exercise, arrhythmia from electrolyte disturbance

131

fabry dz

XR. sphingolipidosis. Sx: peripheral neuropathy of hands/feet, angiokeratomas, CV/renal dz. deficient enzyme: alpha-galactosidase A. accumulate: ceramide trihexoside

132

gaucher dz

AR. most common. Sx: HSM, pancytopenia, osteoporosis, aseptic necrosis of femur, bone crises, gaucher cells (lipid-laden macrophages that look like crumpled tissue paper). Tx: recombinant glucocerebrosidase. deficient enzyme: glucocerebrosidase (beta-glucosidase). accumulate: glucocerebroside. inc. in ashkenazi

133

niemann-pick dz

AR. sphingolipidosis. Sx: progressive neurodegeneration, HSM, foam cells, cherry-red macula. deficient enzyme: sphingomyelinase. accumulate: sphingomyelin. inc. in ashkenazi

134

tay-sachs dz

AR. sphingolipidosis. Sx: progressive neurodegeneration, dev. delay, cherry-red macula, lysosomes w/onion skin, NO HSM. deficient enzyme: hexosaminidase A. accumulate: GM2 ganglioside. inc. in ashkenazi

135

krabbe dz

AR. sphingolipidosis. Sx: peripheral neuropathy, dev. delay, optic atrophy, globoid cells. deficient enzyme: galactocerebrosidase. accumulate: galactocerebroside, psychosine

136

metachromatic leukodystrophy

AR. sphingolipidosis. Sx: central and peripheral demyelination w/ataxia, dementia. deficient enzyme: arylsulfatase A. accumulate: cerebroside sulfate

137

hurler syndrome

AR. mucopolysaccharidosis. Sx: dev. delay, gargoylism, airway obstruction, corneal clouding, HSM. deficient enzyme: alpha-L-iduronidase. accumulate: heparan sulfate, dermatan sulfate

138

hunter syndrome

XR. mucopolysaccharidosis. Sx: mild hurler + agressive behavior. NO corneal clouding. deficient enzyme: deparan sulfate, dermatan sulfate

139

lysosomal storage mnemonics

No man picks his nose w/his sphinger. tay-saX lacks heXosaminidase. hunters see clearly and aggressively aim for the X.

140

fatty acid synthesis

SYtrate: SYnthesis. requires citrate transport from mitochondria to cytosol. occurs mostly in liver, lactating mammary glands, and adipose tissue. biotin = cofactor.

141

fatty acid degradation

CARnitine: CARnage of fatty acids. long-chain FA degradation requires carnitine-dependent transport into mitochondrial matrix.

142

systemic primary carnitine deficiency

inherited defect in LCFA transport into mitochondria -> toxic accumulations -> weakness, hypotonia, kypoketotic hypoglycemia

143

medium-chain acyl-CoA dehydrogenase deficiency

AR d/o of fatty acid oxidation -> dec. ability to break down FA -> acetyl-CoA -> accumulation of 8-10C fatty acyl carnitines in blood and hypoketotic hypoglycemia. presents in infancy or early childhood w/vomiting, lethargy, seizures, coma, and liver dysfxn. minor illness can -> sudden death so don't fast!

144

ketone bodies

liver metabolizes FAs and AAs -> acetoacetate and beta-hydroxybutyrate to fuel muscle and brain. in starvation and DKA, oxaloacetate is depleted for gluconeogenesis. in alcoholism, excess NADH shunts oxaloacetate -> malate. both -> ateyl-CoA buildup, shunting glucose and FFAs -> ketone production. urine test for ketones doesn't detect beta-hydroxybutyrate

145

fasting priorities

supply glucose to the brain and RBCs, preserve protein

146

fed state

glycolysis and aerobic respiration. insulin stimulates storage of lipids, proteins, and glycogen

147

fasting state

hepatic glycogenolysis (major); hepatic gluconeogenesis, adipose release of FFAs (minor. glucagon and epinephrine stimulate use of fuel reserves

148

starvation days 1-3

blood glucose maintained by: hepatic glycogenolysis, adipose release of FFAs, muscle and liver shift fuel use from glucose to FFA, hepatic gluconeogenesis for peripheral tissue lactate and alanine and propionyl-CoA (from odd chain FAs). glycogen reserves only last 1 day. RBCs have no mitochondria - can't use ketones.

149

starvation days 3+

adipose stores (ketones become main fuel for brain). after these are depleted, vital protein degradation accelerates -> organ failure + death. amount stored determines survival time.

150

cholesterol

needed to maintain cell membrane integrity and to synthesize bile acid, steroids, and vit D

151

cholesterol synthesis

rate-limiting step is catalyzed by HMG-CoA reductase (induced by insulin), which converts HMG-CoA -> mevalonate. 2/3 of plasma cholesterol = esterified by lecithin-cholesterol acyltransferase (LCAT)

152

statin MoA

competitively and reversibly inhibit HMG-CoA reductase

153

pancreatic lipase

degradation of dietary TGs in small intestine

154

lipoprotein lipase (LPL)

degradation of TGs circulating in chylomicrons and VLDLs. found on vascular endothelial surface

155

hepatic TG lipase (HL)

degradation of TGs remaining in IDL

156

hormone-sensitive lipase

degradation of TGs stored in adipocytes

157

LCAT

catalyzes cholesterol esterification

158

cholesterol ester transfer protein (CETP)

mediates transfer of cholesterol esters to other lipoprotein particles

159

apolipoprotein E

mediates remnant uptake. used by chylomicrons, chylomicron remnants, VLDL, IDL, and HDL (not LDL)

160

apolipoprotein A-I

activates LCAT. used by chylomicrons and HDL

161

apolipoprotein C-II

lipoprotein lipase cofactor. used by chylomicrons and VLDL

162

apolipoprotein B-48

mediates chylomicron secretion. used by chylomicrons and chylomicron remnants

163

apolipoprotein B-100

binds LDL receptor. used by VLDL, IDL, and LDL

164

lipoprotein fxns

composed of varying proportions of cholesterol, TGs, and phospholipids. LDL and HDL carry the most cholesterol. LDL transports cholesterol from liver -> tissues. HDL transports cholesterol from periphery to liver.

165

chylomicron

delivers dietary TGs to peripheral tissue. delivers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their TGs. secreted by intestinal epithelial cells.

166

VLDL

delivers hepatic TGs to peripheral tissue. secreted by liver.

167

IDL

formed in the degradation of VLDL. delivers TGs and cholesterol to liver

168

LDL

delivers hepatic cholesterol to peripheral tissues. formed by hepatic lipase modification of IDL in peripheral tissue. taken up by target cells via receptor-medicated endocytosis.

169

HDL

mediates reverse cholesterol transport from periphery to liver. acts as a repository for apolipoproteins C and E (which are needed for chylomicron and VLDL metabolism). secreted from both liver and intestine. EtOH -> inc. synthesis.

170

I: hyperchylomicronemia

AR. lipoprotein lipase deficiency or altered apolipoprotein C-II -> increased chylomicrons, TGs, and cholesterol in the blood -> pancreatitis, HSM, eruptive/pruritic xanthomas. NO inc. risk of atherosclerosis. creamy layer in supernatant.

171

IIa: familial hypercholesterolemia

AD. absent or defective LDL receptors -> inc. LDL and cholesterol in blood -> accelerated atherosclerosis (may have MI before 20), tendon xanthomas, and corneal arcus. heterozygotes (1:500) have cholesterol ~300. homozygotes (very rare) have cholesterol ~700.

172

IV: hypertriglyceridemia

AD. hepatic overproduction of VLDL -> inc. VLDL and TGs in blood. TG level >100 can cause acute pancreatitis