Ch. 15: Protein & a.a. Metabolism Flashcards Preview

Medical Biochemistry > Ch. 15: Protein & a.a. Metabolism > Flashcards

Flashcards in Ch. 15: Protein & a.a. Metabolism Deck (114):
1

Why are His and Arg conditionally essential?

Required for optimal development & growth in infants

His essential for uremia pts (problem w/inflammation)

2

In liver dysfunction, which a.a. become essential?

Cys & Tyr
(Cannot convert Met ➡️ Cys or Phe ➡️ Tyr)

3

What is the metabolite of melamine? What problems can they cause?

Cyanuric acid

Form stones in kidneys ➡️ acute renal failure in infants

4

Why is it important to maintain nitrogen balance?

Absence of a.a. ➡️ pro synthesis stops, catabolism of unused a.a. ➡️ ⬆️ N loss in urine, ⬇️ growth

5

What is normal N balance? Negative? Positive?

Normal: Dietary intake of N = N loss
Negative: Dietary intake of N < N loss
Positive: Dietary intake of N > N loss

6

How are a.a. transported into cells?

Against concentration gradient

Semi-active process: coupled to Na+ dependent carrier system

7

What are the 5 a.a. transport systems in kidney & intestine?

1) Neutral
2) Acidic
3) Basic
4) Ornithine & cystine
5) Gly & Pro

8

Examples of inherited defects in a.a. transport?

1) Hartnup disease (neutral a.a.)
2) Cystinuria (cystine in urine)
3) Cystinosis (systemic cystine)

9

Effect of deficiency in GSH synthetase? (In gamma-glutamyl cycle for a.a. transport)

Accumulation of 5-oxoproline ➡️ excreted into urine ➡️ 5-oxoprolinuria

10

4 types of deamination reactions? Which is most important? Examples?

1) oxidative deamination (most important)
2) direct deamination: His
3) hydrolytic deamination: Asn, Gln
4) dehydrolytic deamination: Ser, Thr

11

4 examples of oxidative deamination? Which is major?

1) Glutamate dehydrogenase (major)
2) L-amino acid oxidase
3) D-amino acid oxidase
4) Monoamine oxidase (MAO)

12

Glutamate DH: metal ion cofactor? Requires what?

Zinc

NAD+ or NADP+

13

⬆️ [Glutamate DH] where?

Mitochondria of liver, heart, muscle, kidney

14

➕ modulators of glutamate DH?

ADP
GDP
some a.a.

15

➖ modulators of Glutamate DH?

ATP
GTP
NADH

16

Overall effect of transamination-deamination rxns depend on?

[substrate]

17

What is produced as by-product in transamination-deamination rxns? What happens to them?

1) NH3 (➡️ detoxified by: conversion to Gln & Asn or urea)

2) NADH (➡️ oxidized by ETC)

18

General steps of L-amino acid oxidase? Products?

Alpha a.a. ➡️ alpha-imino acid ➡️ alpha-keto acid
(Same enzyme at each step)

Alpha-keto acids, H2O2, NH4+

19

General steps of D-amino acid oxidase? Products? Where is this found?

Glycine ➡️ alpha-imino acid ➡️ glyoxylate
(Same enzyme each step)

Glyoxylate, H2O2, NH4+

Bacteria in gut (humans can't have D-a.a. in body)

20

Steps of conversion from D-amino acids ➡️ L-amino acids? Enzymes?

D-a.a. ➡️ alpha-keto acid (D-a.a. Oxidase)

Alpha-keto acid ➡️ L-a.a. (Reamination via transaminase)

21

Norepinephrine (monoamine) ➡️ ? (via MAO)

Co-factors?

DOPGAL

FAD (➡️ FADH2)
H2O (➡️ NH4+)

22

2 possible products made from DOPGAL? Enzymes for each rxn?

1) DOPGAL ➡️ DOPEG (glycol) (aldehyde reductase)
2) DOPGAL ➡️ DOMA (acid) (aldehyde dehydrogenase)

23

General steps of dehydrolytic deamination?

Enzymes, co-factors?

Ser, Thr, or Homoserine ➡️ alpha-imino acid ➡️ alpha-keto acid

1) Uses specific dehydratase + pyridoxal P (H2O out)
2) NH3 out, H2O in

24

What is the most abundant a.a. in body? What synthesizes it?

Glutamine

Gln synthetase

25

Main steps of glu-gln cycle? (Using glu as neurotransmitter & recycle)

Signal ➡️ gln ➡️ glu (via glutaminase) ➡️ released ➡️ recycled back to gln (via gln synthetase)

26

What co-factor is important in transamination-aminotransfer rxns?

How is it bound to its apoenzyme?

Pyridoxal P

Carbonyl C reacts with epsilon-amino group of lysine residue ➡️ Schiff base

27

Important transamination-aminotransfer reaction?

a.a. + alpha-KG ➡️ alpha-keto acid + glu

28

All a.a. participate in transamination rxn EXCEPT?

Lys
Thr
Pro
OH-Pro

29

Alanine aminotransferase (ALT) same as? Substrates ➡️ products?

Glutamate pyruvate aminotransferase (GPT)

Ala + alpha-KG ➡️ pyruvate + glu

30

Aspartate aminotransferase (AST) same as? Substrates ➡️ products?

Glutamate oxaloacetate aminotransferase (GOT)

Asp + alpha-KG ➡️ oxaloacetate + Glu

31

Inhibitors of pyridoxal P? What do these cause?

Isonicotinic acid hydrazide
Hydralazine
Cycloserine

Inhibit transamination

32

Role of liver in a.a. metabolism?

1) Oxidize all a.a. EXCEPT BCAAs
2) a.a. Synthesis
3) urea synthesis

33

Role of skeletal muscle in a.a. metabolism?

1) metabolize ala, asp, glu, BCAAs
2) release ala, gln

34

Role of small intestine in a.a. metabolism?

1) metabolize dietary gln, glu, asn, asp ➡️ CO2 & H2O or lactate, ala, citrulline, NH3

35

Role of kidneys in a.a. metabolism?

1) release ser, ala
2) take up gln, pro, gly
3) acid/base regulation
4) alpha-KG ➡️ glucose or oxidized

36

Role of brain in a.a. metabolism?

1) take up BCAAs
2) glu-gln cycle
3) asp & gly = neurotransmitters
4) glu ➡️ GABA
5) tyr ➡️ dopamine, norepi, epi
6) trp ➡️ serotonin

37

How does brain use CHO, a.a., and lipids?

CHO: major fuel

a.a. & lipids: for major fxns

38

NH3 toxic to brain (not other tissues) ➡️ why?

1) Hydrophobic: interferes w/membrane integrity, signal transduction
2) Depletes glu (needed as neurotransmitter)
3) Depletes TCA cycle intermediates

39

How does NH3 cause anorexia, sleep disturbances, & pain insensitivity?

⬆️ trp transport across BBB & accumulation of its metabolites (serotonin, quinolinic acid)

40

Urea synthesis: where do the 2 N come from?

What is the precursor for both N?

1) free NH3
2) Asp

Glu: (1) by Glu DH, (2) by AST

41

How much ATP consumed in urea synthesis?

4 ATP

42

Where is urea formed? ➡️ urine?

Made in liver ➡️ kidneys ➡️ urine

43

What is the rate-limiting step of urea synthesis in hepatocytes?

Enzyme?

1st step: NH4+ + CO2 ➡️ carbamoyl P

Carbamoyl P synthase I (CPS I)

44

What substrate stimulates rate-limiting step of urea cycle?

How is it formed? What ➕ and ➖ this rxn?

N-acetylglutamate

Acetyl-CoA + glu (via N-acetylglutamate synthase)
➕: Arg
➖: N-acetylglutamate

45

Where in hepatocyte does urea cycle take place?

Mitochondrial matrix: carbamoyl P + ornithine ➡️ citrulline

Cytosol: citrulline moved out of MT ➡️ rest of cycle ➡️ ornithine moves into MT

46

Which enzyme in urea cycle is only found in liver? Fxn?

Arginase

Arginine + H2O ➡️ ornithine + urea

47

CPS I: cellular location? Pathway involved? Source of nitrogen?

Mitochondria

Urea cycle

Ammonia

48

CPS II: cellular location? Pathway involved? Source of nitrogen?

Cytosol

Pyrimidine synthesis

Gamma-amide group of gln

49

3 fates of fumarate: to TCA cycle?

Fumarate ➡️ malate ➡️ MT ➡️ TCA cycle

50

3 fates of fumarate: to urea cycle?

Fumarate ➡️ malate ➡️ OAA (via malate DH) ➡️ asp ➡️ urea cycle

51

3 fates of fumarate: to glucose? (Major)

Fumarate ➡️ malate ➡️ OAA (via malate DH) ➡️ PEP ➡️ glucose

52

3 causes of hyperammonemia?

1) inborn errors of ureagenesis & organic acidemias
2) liver immaturity (transient HA of newborn)
3) liver failure (hepatic encephalopathy)

53

OCT enzyme deficiency: how is it diagnosed? What does it cause?

Allopurinol

Blocks pyrimidine synthesis ➡️ Orotidinuria (⬆️ orotidine in urine)

54

Sodium benzoate: leads to? How many N lost?

Elimination of hippurate (benzoylglycine)

1 N

55

Phenylacetate or phenylbutyrate: leads to? How many N lost?

⬆️ excretion of phenylacetylglutamine

2 N

56

If NAGS enzyme deficiency, what can be given to activate CPS I?

N-carbamoylglutamate

57

What is the most common cause of hyperammonemia in adults?

Liver disease (due to ethanol abuse, infection, cancer) ➡️ ⬇️ ability to detox NH3

58

How are non-essential a.a. synthesized?

From carbon skeletons from lipid & CHO sources

From transformations involving essential a.a.

59

Precursors of: glu, asp, ser, gly, tyr?

Alpha-ketoglutaric acid
Oxalo-acetic acid
3-phospho-glyceric acid
Ser
Phe

60

Precursors of: pro, ala, cys, arg, gln, asn?

Glu
Pyruvic acid
Met & Ser
Glutamate-gamma-semialdehyde
Glu
Asp

61

Arg is a precursor for which metabolites?

NO
Phosphocreatine
Spermine
Ornithine

62

Arg ➡️ citrulline

Enzyme? Co-factors?

NO synthase

FMN, FAD, BH4, Fe2+, heme complex

63

How does NO cause vasodilation?

➕ modulator of guanylate cyclase (converts GTP ➡️ cGMP)

cGMP ➡️ smooth muscle relaxation

64

Which a.a. is gly converted to?

What type of metabolism is this?

Ser

One carbon metabolism

65

Disorders of glycine metabolism: nonketotic hyperglycinemia?

Inborn error due to defect in gly cleavage enzyme complex ➡️ ⬆️ gly in body fluids (CSF)

66

Disorders of gly metabolism: ketotic hyperglycinemia?

Occurs in propionic acidemia (dysfxn of CoA metabolism ➡️ ketone bodies generated)

67

Disorders of gly metabolism: primary hyperoxaluria type I?

Deficiency of cytosolic alpha-ketoglutarate-glyoxylate carboligase ➡️ ⬆️ glyoxylate ➡️ converted to oxalate (forms crystals)

68

Creatine synthesis requires which 3 a.a.?

Arg, gly, SAM (S-adenosyl-homocysteine)

69

3 diff products obtained from Ser?

3PG
Pyruvate
Gly

70

Proline metabolism disorders: Ornithinemia?

Ornithine aminotransaminase deficiency

71

Proline metabolism disorders: hyperprolinemia?

Proline oxidase deficiency

72

Proline metabolism disorders: hydroxyprolinemia?

Hydroxyproline oxidase deficiency

73

Folate deficiency ➡️ accumulation of? (Synthesized from which a.a. ?)

What other deficiencies cause this accumulation?

FiGlu (N-Formiminoglutamate)

His

Vit B12, Glu formimino-transferase deficiencies

74

Important fxn of branch-chained a.a. metabolism?

Yield high energy (amino fats)

75

What DH complex also similar to PDH and alpha-KG DH?

BCKADH (branched-chain alpha-ketoacid DH)

E1 diff, E2 & E3 same

76

Products from Leu metabolism?

Acetoacetate

Acetyl CoA

77

Products from Ile metabolism?

Propionyl CoA

Acetyl-CoA

78

Product of Val metabolism? Requires which cofactor at which step?

Succinyl CoA

Vit B12 (methylmalonyl CoA ➡️ Succinyl CoA)

79

Main fxn of SAM?

Methyl donor (in protein & cysteine synthesis)

80

Which vit needed to methylated homocysteine ➡️ methionine?

Vit B12

(Methyl donor is N5-methyl H4 folate)

81

CH3 transfer rxn w/SAM ➡️ SAH

acceptor: guanidinoacetic acid ➡️ ?

Creatine

82

CH3 transfer rxn w/SAM ➡️ SAH

acceptor: nicotinamide ➡️ ?

N-methylnicotinamide

83

CH3 transfer rxn w/SAM ➡️ SAH

acceptor: norepi ➡️ ?

Epi

84

CH3 transfer rxn w/SAM ➡️ SAH

acceptor: phosphatidylethanolamine ➡️ ?

Phosphatidylcholine (3 rounds of methylation)

85

CH3 transfer rxn w/SAM ➡️ SAH

acceptor: N-acetyl-serotonin ➡️ ?

Melatonin

86

How does Cys regulate its own formation?

Acts as allosteric ➖ of cysteine gamma lase (?)

87

Cys required to form which products?

Glutathione

CoA-SH

88

Major end products of Cys metabolism?

Taurine: conjugated w/bile in liver ➡️ excreted by kidneys

Sulfate: converted to PAPS (sulfate donor)

Pyruvate

89

Abnormalities involving sulfur-containing a.a.:

Hypermethioninemia: which enzyme deficient?

Met adenosyltransferase

90

Abnormalities involving sulfur-containing a.a.:

Hypermethioninemia, hyperhomocysteinemia, homocystinuria: which enzyme deficient?

Cystathionine beta-synthase

91

Abnormalities involving sulfur-containing a.a.:

Homocystinuria: which vitamins are deficient?

Folate
Vit B12

92

Abnormalities involving sulfur-containing a.a.:

Cystathioninuria: which enzyme deficient?

Cystathionine gamma-lyase

93

Abnormalities involving sulfur-containing a.a.:

Cerebral atrophy, lens dislocation: which enzyme deficient?

Hereditary sulfate oxidase

94

Abnormalities involving sulfur-containing a.a.:

Cystinuria: disorder with what transport?

Renal or GI a.a. transport disorder

95

Abnormalities involving sulfur-containing a.a.:

Cystinosis: which transport defective? Causes what?

ATP-dependent cystine efflux from lysosomes ➡️ cystine crystals deposited in tissues

96

Which 4 vitamins are required in homocysteine metabolism?

FH4
Vit B12
Pyridoxine
Riboflavin

97

What causes hyperhomocysteinemia?

Def of enzymes in homocysteine remethylation / transsulfuration pathways

98

What are clinical manifestations of severe hyperhomocysteinemia? (Due to genetic defect in which enzyme?)

cystathionine beta-synthase

Atherosclerosis, thromboembolic complications, skeletal abnormalities, ectopia lentis, mental retardation

99

Metabolism of homocysteine: steps to enter FH4 into pathway?

Enzymes?

Folate ➡️ FH4 (dihydrofolate reductase, 2 NADPH)
FH4 + Ser➡️ methylene FH4 + gly (ser OHmethyl transferase, vit B6)
Methylene FH4 ➡️ Methyl FH4 (MTHFR)
Methyl FH4 + homocysteine ➡️ met

100

What inhibits conversion of folate ➡️ FH4?

Methyltrexate

101

Steps of methylation cycle of homocysteine metabolism?

Enzyme & co-factor needed in methylation of homocysteine?

Met + ATP ➡️ SAM ➡️ SAH ➡️ homocysteine + methyl FH4 ➡️ Met

Methyl transferase (methylcobalamin)

102

Phe hydroxylase: where found? Requires what co-factors?

What other enzyme is needed in tyr & trp hydroxylation?

Liver, kidneys

BH4, NADPH

Dihydropteridine reductase

103

PKU: deficiency of what enzymes/co-factors?

Phe hydroxylase, BH4, dihydropteridine reductase

104

PKU: what accumulates in urine? How is it generated?

How many types of PKU are there?

Phenylpyruvate
Phe ➡️ phenylpyruvate (transaminase)

Types I, II, III

105

Phe ➡️ Tyr: involves BH4 ➡️ quinonoid-dihydrobiopterin

Major path to regain BH4? Minor path?

Direct via Dihydropteridine reductase + NADPH

With intermediate (7,8-dihydrobiopterin) via dihydrofolate reductase

106

Deficiency of what enzyme ➡️ alkaptonuria?

Involved in metabolism of what a.a.?

What builds up in urine ➡️ black pee

Homogentisic acid oxidase

Phe, Tyr

Homogentisic acid (oxidized w/air exposure)

107

Phe & Tyr are precursors for what?

T4, melanin, norepi, epi

108

Melanin is precursor to synthesize what?

Eumelanins

109

Abnormalities of tyr metabolism: Tyrosinemia type II

Deficiency in which enzyme? Leads to what conditions?

Hepatic cytosolic tyr aminotransferase

Hypertyrosinemia, tyrosinuria

110

Abnormalities of tyr metabolism: Tyrosinosis

Deficiency of what enzyme? Leads to what conditions?

Fumarylacetoacetate hydrolase

Abnormal liver fxn, renal tubular dysfxn, anemia, vit D-resistant rickets

111

Abnormalities of tyr metabolism: Albinism

Cause? Some forms are from deficiency in what enzyme?

Lack of melanin production (hypomelanosis)

Tyrosinase

112

Trp is involved in synthesis of what?

Nicotinic acid (amide): needed for NAD+ and NADP+ synthesis
5-hydroxytryptamine (serotonin)
Melatonin
Formate

113

Abnormalities of Trp metabolism: carcinoid tumor?

⬆️ serotonin synthesis

114

Abnormalities of Trp metabolism: Hartnup disease?

Disorder of renal tubular, intestinal absorption of Trp & other neutral a.a.