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Flashcards in Biochem - metabolism Deck (56):
1

Metabolism that happens specifically in mitochondria

Fatty acid oxidation
acetyl-Coa production
TCA cycle
oxidative phosphorylation
ketogenesis

2

ATP production in malate-aspartate shuttle vs. G3P shuttle

Electrons moved to ETC b/c NADH can't cross membrane

Malate-aspartate shuttle: utilizes malate, creates 32 ATP (heart, liver)

G3P shuttle: utilizes G3P, creates 30 ATP since electrons delivered directly to complex 2 (skeletal muscle)

3

Key enzymes in glycolysis

Hexokinase/glucokinase

PFK-1 (incr. by F26BP)

Pyruvate kinase

4

Regulation by F26BP

incr. F26BP = more glycolysis, less gluconeogenesis

less F26BP = less glycolysis

5

Two complexes in glycolysis and TCA cycle that are similar

Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase

use same cofactors, similar substrates and actions

6

PDH complex deficiency

X-linked, causes pyruvate shunting to lactate and alanine starting in infancy

tx: incr. lysine/leucine intake! ketogenic nutrients/high fat content

7

Four possible endpoints for pyruvate

1.) alanine: ALT, B6

2.) oxaloacetate: pyruvate carboxylase, biotin

3.) acetyl-CoA: PDH, B1/2/3/5

4.) lactate: LDH, B3

8

ETC inhibitors

decr. proton gradient

cyanide, carbon monoxide, antimycin A, rotenone

9

Uncoupling agents

Disconnects ETC from O2 consumption

Generates free heat

2,4-dinitrophenol (weight loss), aspirin, thermogenin

10

Four main gluconeogenesis enzymes

Pyruvate carboxylase (makes oxaloacetate)
PEP carboxykinase (OAA to PEP)
Fructose-1,6-bisphosphatase
Glucose-6-phosphatase

11

Odd-chain fatty acids

produce 1 propionyl-CoA, which enters TCA, then gluconeogenesis, thus a source of glucose

12

Uses of NADPH

glutathione reduction in RBCs
fatty acid and cholesterol/steroid synthesis

13

Location of HMP shunt

RBCs (glutathione reduction

lactating mammary glands, liver, adrenal cortex (fatty acid/steroid synthesis)

14

G6P DH deficiency

decr. NADPH in RBCs

hemolysis precipitated by oxidizing agents or infections (from inflammatory response)

random: incr. malarial resistance

15

Fructokinase vs. aldolase B deficiency

Essential fructosuria - asx

Fructose intolerance - incr. F-1-P, decr. free PO4, decr. GNG. Sx present after sugar consumption (jaundice, cirrhosis, vomiting), incr. fructose in urine

16

Galactokinase vs. galactose-1-phosphate uridyltransferase deficiency

Galactokinase deficiency - mild condition, infantile cataracts

Classic galactosemia - failure to thrive, jaundice, hepatomegaly, ID, E. coli sepsis

17

Enzymes in sorbitol metabolism

Aldose reducatase: glucose to sorbitol

Sorbitol dehydrogenase: sorbitol to fructose

18

Aldose reductase only locations

Schwann cells, retina, kidneys, lens

19

Findings in lactase deficiency

Stool: decr. in pH

Breath: incr. H content

20

Urea cycle key steps

Carbamoyl phosphate: in mito, converts CO2 + NH3 to carbamoyl phosphate
OTC: combines CP with ornithine to make citrulline
Citrulline + aspartate/ATP = argininosuccinate
Loss of fumarate = arginine
Arginase makes ornithine again! This is loss of UREA

21

Components of urea

1 NH3
1 CO2
1 Aspartate

22

Path of ammonia from amino acids to excretion

Muscle: amino acids --> glutamate --> alanine

Cori or Cahill cycle: muscle to liver (requires alanine and lactate)

Liver: alanine --> glutamate --> urea

23

Urea cycle deficiencies

N-acetylglutamate synthase deficiency: leads to hyperammonemia (required cofactor for carbamoyl phosphate synthetase)

OTC deficiency: X-linked recessive, look for orotic aciduria w/o megaloblastic anemia

24

Defects in amino acid metabolism

Phenylketonuria
Maple syrup urine disease
Alkaptonuria
Homocystinuria
Cystinuria

25

Intellectual disability, seizures, fair skin, musty body odor

Phenylketonuria - decr. phenylalanine hydroxylase (decr. Phe to Tyr)

tx: tyrosine supplementation, avoid aspartame (Phe)

26

Severe CNS defects, death, urine smells like burnt sugar

Maple syrup urine disease - blocked degradation of branched amino acids (isoleucine, leucine, valine)

decr. alpha-ketoacid dehydrogenase

tx: thiamine supplementation and restrict isoleucine, leucine, valine in diet

27

Dark connective tissue, brown sclerae, urine turns black on expsoure to air

Alkaptonuria - def. of homogentisate oxidase in the degradative pathway of tyrosine to fumarate

Homogentisic acid accumulates in tissues

28

Osteoporosis, marfanoid habitus, kyphosis, lens subluxation

Homocystinuria

-- cystathione synthase (B6 enzyme) deficiency (leads to decr. cysteine and incr. methionine)
-- homocysteine methyltransferase (B12 enzyme) deficiency (leads to decr. methionine)

29

Recurrent hexagonal kidney stones, positive urinary cyanide-nitroprusside test

Cystinuria - defect in renal PCT/intestinal reabsorption of Cysteine, Ornitihine, Lysine, Arginine

tx: potassium citrate/acetazolomide, chelating agents

30

Homocyteine products

Homocysteine methyltransferase - converts to methionine using B12

Cystathione synthase - converts to cystathione using B6

31

Stimulators of glycogenolysis

Glucagon (incr. cAMP, PKA)
Epinephrine alpha and beta receptors (incr. cAMP, PKA)

32

Stimulators of glycogen synthesis

Insulin (tyrosine kinase receptor, phosphorylation of glycogen synthase)

33

Glycogen breakdown

Muscle - glycogen to G6P (uses phosphoglucomutase) to enter glycolysis

Liver - Glycogen phosphorylase, debranching enzymes cleaves off in orderly pattern

34

Glycogen storage diseases

Type I: Von gierke (glucose-6-phosphatase)
Type II: Pompe (acid maltase)
Type III: Cori (debranching)
Type IV: McArdle (skeletal muscle glycogen phosphorylase)

35

Severe fasting hypoglycemia, incr. glycogen in liver (hepatomegaly), incr. TGs, lactic acidemia

Von gierke - glucose-6-phosphatase

tx: frequent oral glucose/cornstarch, avoid fructose/galactose

36

Hypertrophic cardiomyopathy, cardiomegaly, exercise intolerance, early death

Pompe - acid maltase

Pompe trashes the pump

37

Fasting hypoglycemia with normal lactate levels

Cori - debranching enzyme

Gluconeogenesis intact

38

Painful muscle cramps, myoglobinuria, arrhythmia from electrolyte disturbances

McArdle (skeletal muscle phosphorylase)

Blood glucose levels are unaffected

McArdle = muscle

Tx: B6 supplementation

39

HSM, pancytopenia, aseptic necrosis of femur, bone crises, Gaucher cell (lipid-laden macs, tissue paper)

Gaucher disease - glucocerebridase

accum of glucocerebroside

40

Progressive neurogeneration, foam cells, cherry-red macula, HSM

Niemann-Pick disease - sphingomyelinase

accum of sphingomyelin

41

Progessive neurodegeneration, developmental delay, cherry-red macula, onion skin lysosomes, NO HSM

Tay-Sachs disease - hexosiaminidase A

NOTE: NO HEPATOMEGALY!

42

Optic atrophy, globoid cells, peripheral neuropathy

Krabbe disease - galactocerebridase

43

Hurler vs. Hunter syndrome

Mucopolysaccharides

Hurler - corneal clouding, airway obstruction
Hunter - no corneal clouding, aggressive behavior

44

Citrate shuttle

used in fatty acid synthesis to move citrate from mitochondria to the cytosol

sytrate = synthesis

45

Carnitine shuttle

used to move fatty acyl-CoA from the cytosol to the mitochondria

carnitine = fatty acyl carnage

46

Minor illness leading sudden death, liver dysfunction, present in infancy or early childhood with vomiting

MCAD deficiency

accumulation of 8 to 10 carbon fatty acyl carnitines in the blood

leads to hypoketotic hypoglycemia***

47

Causes of ketogenesis

prolonged starvation or diabetes - depletion of oxaloacetate for gluconeogenesis

alcoholism - excess NADH shunts oxaloacetate to malate

48

Fat sources for gluconeogenesis

Odd-chain FFAs

Adipose tissue glycerol

49

LPP that mediates remnant uptake (extra remnantsq

Apo-E

50

LPP that activates LCAT

Apo-A1

51

LPP that serve as lipoprotein lipase cofactor

Apo-C2

52

LPP that mediates chylomicron secretion

Apo-B48

53

LPP that binds LDL receptor

Apo-B100

54

Xanthomas, pancreatitis, HSM, creamy layer in supernatant

Type I hyperchylomicronemia

lipoprotein lipase deficiency

55

Accelerated atherosclerosis, tendon xanthoma, corneal arcus

Type II hypercholesterolemia

absent/defective LDL receptor

56

Hepatic overproduction of VLDL

Type IV hypertriglyceridemia