Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Biochem - Exam 2 > N metabolism and Urea Cycle > Flashcards

N metabolism and Urea Cycle Flashcards

1
Q

what are aa’s catabolized to?

A

urea + CO2 + H2O

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

aa’s are used in the biosynthesis of what special molecules?

A
  • porphyrins
  • purines and pyrimidines
  • NO
  • melanin
  • hormones, neurotransmitters
  • creatine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

zymogens

A

inactive enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what does the stomach secrete for protein digestion?

A
  • HCl

- pepsinogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is HCl secreted by?

A

parietal cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is low HCl called and what does it cause?

A

achlorhydria - iron deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is pepsinogen secreted by?

A

chief cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

how is pepsinogen turned into pepsin?

A

autocatalytic activation by conformational change at low pH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

action of active pepsin

A

endopeptidase - cleaving peptide bonds to produce smaller peptides and some free aa’s
-prefers CO group provided by an aromatic or acidic aa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what enzymes does the pancreas secrete for protein digestion? how are they activated?

A

zymogens activated by proteolysis:

  • trypsinogen -> trypsin
  • chymotrypsinogen -> chymotrypsin
  • proelastase -> elastase
  • procarboxypeptidases -> carboxypeptidase A or B
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what converts trypsinogen -> trypsin?

A

enteropeptidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what converts chymotrypsinogen -> chymotrypsin?

A

trypsin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what converts proelastase -> elastase?

A

trypsin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what converts procarboxypeptidases -> carboxypeptidase A and B?

A

trypsin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

pancreatic enzymes: which have endopeptidase activity and which have exopeptidase activity?

A

endo: trypsin, chymotrypsin, elastase
exo: carboxypeptidase A and B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

where does trypsin cut?

A

after Arg, Lys (positive)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

where does chymotrypsin cut?

A

after Trp, Tyr, Phe, Met, Leu (aromatics + randoms)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

where does elastase cut?

A

after Ala, Gly, Ser

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

where does carboxypeptidase A cut?

A

before Ala, Ile, Leu, Val

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

where does carboxypeptidase B cut?

A

before Arg, Lys

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

how are aa’s absorbed?

A

semispecific Na+ transport proteins w/ at least 6 types of carriers (aa’s brought into cell with Na+ - symport)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what do defective transporters in aa absorption result in?

A

malabsorption from intestine and decreased resorption from glomerular filtrate -> Hartnup disease, cystinuria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what disease is caused by defective neutral aa transporters?

A

Hartnup disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is the mutation in Hartnup disease?

A

mutation in Na-dependent and Cl-independent neutral aa transporter, which is expressed predominantly in the intestine and kidneys

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

how is Hartnup disease passed down?

A

autosomal recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

symptoms of Hartnup disease

A
  • ataxia
  • emotional instability
  • pellagra rash (due to B3)
  • neutral amidoaciduria
  • high urine levels of neutral aa
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what are most symptoms of Hartnup believed to be caused by?

A

niacin deficiency - need tryptophan to synthesize niacin, and with Hartnups, you can’t absorb tryptophan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what disease is caused by defective dibasic aa transporters?

A

cystinuria - also transport cystine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what is cystinuria?

A

cystine stones in bladder and kidneys

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

describe intracellular proteolysis of body proteins

A
  • lysosomes: acid hydrolases, pH 5 optimum

- cytosol: proteins tagged with ubiquitin for degradation by 26S proteasome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

describe extracellular proteolysis of body proteins

A
  • serine proteases

- matrix metalloproteases (collagenases)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what can elastase from neutrophils contribute to clinically?

A

lung damage in chronic obstructive pulmonary disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what can matrix metalloproteases contribute to clinically?

A

metastasis of cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

how does the body deal with N formed from aa breakdown?

A
  • blood: travels as aa’s (Ala, Glu)

- liver: efficiently detoxifies NH4, forms urea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

what is the only organ that has all enzymes for urea synthesis?

A

liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

why does the body form urea?

A

major way body gets rid of ammonia

  • soluble
  • not charged (doesn’t change pH of fluids)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

structure of urea

A

H2N -C(=O) -NH2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

equilibrium for ammonia in body and pK value

A

NH3 + H+ NH4 pk = 9.3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

problem with ammonia in body

A

ammonia (in equilibrium w/ NH4+) is very toxic to CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

how is the problem with ammonia dealt with?

A

ammonia + ammonium converted to two nontoxic compounds: urea and glutamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

what is the first step in aa catabolism?

A

remove amino groups

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

two ways to remove the amino group from an aa?

A
  1. transamination

2. deamination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

transamination

A

aminotransferase/transaminase moves alpha amino groups to an alpha-ketoacid to form glutamate, which is either used or deaminated, releasing an NH4+ (reversible rxn)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

deamination

A

direct release of NH4+ - different methods for different aa’s:

  • glutamate DH
  • hydrolytic deamination (e.g. glutaminase)
  • non-oxidative (PLP dependent)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

what cofactor does transamination require?

A

PLP (pyridoxal phosphate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

reaction catalyzed by aspartate aminotransferases (AST)

A

Asp + alpha-ketoglutarate -> OAA + Glu

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

reaction catalyzed by alanine aminotransferase (ALT)

A

Ala + alpha-ketoglutarate -> pyruvate + Glu

48
Q

why are AST and ALT important clinically?

A

serum levels used to evaluate for liver damage (especially for industrial solvents - chloroform, carbon tetrachloride)

49
Q

where is PLP derived from?

A

vitamin B6

50
Q

what reactions most commonly are associated with using PLP?

A

transaminations and deaminations - but also used for many other reactions (like glycogen phosphorylase)

51
Q

business end of PLP?

A

aldehyde carbon forms a Schiff base (C=N)

52
Q

three methods of deamination

A
  1. oxidative deamination
  2. hydrolytic deamination
  3. non-oxidative deamination (PLP dependent)
53
Q

oxidative deamination

A

Glu DH: glutamate -> alpha-ketoglutarate + H+

  • forms NAD(P)H from NAD(P), releases NH4+
  • reversible
54
Q

where does Glu DH rxn take place?

A

liver and mitochondria

55
Q

inhibition of Glu DH

A

GTP, ATP - allosteric

56
Q

activation of Glu DH

A

GDP, ADP - low energy increases aa breakdown to provide alpha-ketoglutarate for TCA

57
Q

hydrolytic deamination

A

done w/ glutaminase or asparaginase on the side chain amide groups of glutamine and asparagine, respectively

58
Q

glutaminase rxn

A

Gln + H2O -> Glu + NH4+

59
Q

where is glutaminase important in the body?

A

kidney - NH4+ forms salts w/ metabolic acids for secretion

60
Q

asparaginase rxn

A

Asn + H2O -> Asp + NH4+

61
Q

non-oxidative deamination

A

done on serine or threonine by serine dehydratase and threonine dehydratase, respectively

62
Q

what does non-oxidative deamination require?

A

PLP

63
Q

serine dehydratase rxn

A

serine -> pyruvate + NH4+

64
Q

threonine dehydratase rxn

A

threonine -> alpha-ketobutyrate + NH4+

65
Q

in non-oxidative deamination, what precedes deamination?

A

dehydration

66
Q

what aa’s transport nitrogen w/i body and where do they take it?

A

Ala and Gln - take N from other tissues to liver or kidney

67
Q

Gln synthetase fxn

A

can fix NH4+ in a carbon compound - one of three human enzymes that can do this

68
Q

what are mutations in Gln synthetase associated with clinically?

A

found in newborns w/ severe brain malformations - large amounts of glutamate in brain (Glu = neurotoxin)

69
Q

pathway of ammonia transport to liver using Gln

A

a-KG -> Glu -> Gln in muscle/peripheral tissues ->

transported to liver -> Gln -> Glu -> a-KG, while NH4+ goes to make urea

70
Q

N balance

A

excreted N = consumed N

-protein content exceeds requirement in normal healthy adult

71
Q

when will you see a positive N balance?

A
  • growing kid
  • pregnant mom
  • during physical trauma
  • -when need to increase protein synthesis, N out < N in
72
Q

when will you see a negative N balance?

A
  • protein malnutrition
  • starvation
  • -body protein degraded to synthesize essential proteins, N out > N in
73
Q

levels of NH4+ in blood

A

25-40 uM normally

74
Q

overall rxn for urea cycle

A

NH4+ + CO2 + Asp + 3ATP + 2H2O –> urea + fumarate + 2ADP + AMP + PPi + 2Pi

75
Q

how many high energy bonds are used for each molecule of urea made?

A

4 - 3 from ATP and one from PPi –> makes the rxn irreversible (large, negative deltaG)

76
Q

origins of each of the parts of urea

A
  • one NH2: from ammonia
  • other NH2: from Asp
  • carbonyl: from HCO3-
77
Q

alternative pathways for forming urea

A

there are none - urea cycle is it

78
Q

what can defects in urea cycle lead to?

A

an increase in NH4+ in blood -> hyperammonemia

79
Q

where does the urea cycle take place?

A

some in cytosol and and some in mitochondria

80
Q

CPS1 product

A

carbamoyl phosphate

81
Q

urea cycle: general pathway

A

ornithine + carbamoyl phosphate -> citrulline -> (+ Asp) -> argininosuccinate -> (release fumarate) -> Arg -> urea + ornithine

82
Q

where does CPS1 function?

A

in mitochondria

83
Q

what cofactor does CPS1 require?

A

NAG (N-acetylglutamate) - allosteric activator

84
Q

what is the rate limiting step for urea cycle?

A

CPS1 (carbamoyl phosphate synthase 1)

85
Q

CPS1 vs. CPS2

A

CPS1: in mitochondria for urea synthesis
CPS2: in cytosol for pyrimidine synthesis

86
Q

where is NAG synthesized?

A

in mitochondria by N-acetylglutamate synthase

Glu + acetyl coA -> NAG

87
Q

NAG synthesis activators

A

Arg

88
Q

which is catalytically active: monomer or dimer of CPS1?

A

monomer of CPS1-NAG

89
Q

what enzyme: citrulline + Asp -> argininosuccinate

A

argininosuccinate synthetase

90
Q

where does the argininosuccinate synthetase rxn take place?

A

cytosol

91
Q

what enzyme: argininosuccinate -> fumarate + arginine

A

argininosuccinate lyase

92
Q

what enzyme: arginine + H2O -> urea + ornithine

A

arginase

93
Q

what enzyme: ornithine + carbamoyl -P -> citrulline

A

ornithine transcarbamoylase (OTC)

94
Q

which urea cycle rxns occur in mitochondria?

A
  • CPS1

- OTC

95
Q

which urea cycle rxns occur in cytosol?

A
  • argininosuccinate synthetase
  • argininosuccinate lyase
  • arginase
96
Q

what does OTC deficiency cause?

A

increased orotate -> carbamoyl-P can’t react w/ OTC , so instead forms pyrimidines

97
Q

what is diagnostic for OTC deficiency?

A

increase in pyrimidines diagnostic for OTC deficiency

98
Q

short term regulation of urea cycle

A

depends on CPS1
(+) NAG - allosteric
(+) protein-rich meal - make more NAG (Km of NAG synthase for Glu is high - not saturated under physiological conditions

99
Q

long term regulation of urea cycle

A

dietary protein levels regulate synthesis of urea cycle enzymes

  • increase protein for days -> increase urea enzyme synthesis -> increase urea excretion
  • reverse for low protein diet
100
Q

starvation and the urea cycle

A

-starvation: increase protein degradation in tissues -> increase synthesis of urea cycle enzymes

101
Q

links b/w urea cycle and TCA

A
  • fumarate
  • OAA:
  • -transamination to Asp
  • -conversion to glucose
  • -condensation w/ acetyl coA to form citrate
  • -conversion into pyruvate
102
Q

what diseases can be caused by autosomal recessive inherited defects of urea cycle?

A
  • HA type I (hyperammonemia)
  • HA type II
  • citrullinemia
  • arginosuccinic aciduria
  • argininemia
103
Q

defect in HA type I and accumulations?

A

CPS1 - NH4+, Gln, Ala

104
Q

defect in HA type II and accumulations?

A

OTC - NH4+, Gln, orotic acid

105
Q

defect in citrullinemia and accumulations?

A

argininosuccinate synthetase - serum citrulline

106
Q

defect in arginosuccinic aciduria and accumulations?

A

argininosuccinate lyase - arginosuccinate

107
Q

defect in argininemia and accumulations?

A

arginase - arginine

108
Q

mechanism of NH4+ toxicity

A

shift in equilibrium of Glu DH rxn toward direction of Glu formation

  • could deplete a-KG (essential for TCA) -> decreased oxidation and ATP production
  • brain: vulnerable to HA since depends on TCA for energy
109
Q

what happens with high levels of Gln in brain?

A
  • osmotic increase in H2O in astrocytes = brain swelling

- increased Gln causes decrease in neurotransmitters Glu and GABA

110
Q

treatment for acute HA

A

hemodialysis or exchange transfusion to rapidly lower ammonia

111
Q

treatment for defects in urea cycle

A
  • limit protein intake in diet
  • remove excess ammonia
  • replace missing intermediates - supplement w/ Arg or citrulline, depending on where defect is
  • future: liver cell supplementation?
112
Q

how do you remove excess ammonia?

A
  • Levulose
  • avoid/treat infections (cell death releases proteins, aa’s)
  • kill intestinal ammonia producing bacteria w/ antibiotics
  • Benzoate and Phenylbutyrate
113
Q

Levulose fxn

A

fructose - bacteria acidifies colon

-promotes excretion of ammonia

114
Q

Benzoate and Phenylbutyrate fxn

A

reduce Gly and Gln levels

115
Q

what drug did Phenylbutyrate replace?

A

Phenylacetate

116
Q

4 ways to circumvent urea cycle defects in N excretion

A
  1. amino groups removed by scavenging aa’s for excretion
  2. benzoic acid removes Gly
  3. forces additional NH3 incorporation into aa synthesis
  4. phenylbutyrate removes Gln (has 2NH3 molecules each)
117
Q

OTC deficiency

A
  • X-linked
  • usually presents in male children/young adults
  • acts like dominant trait in het females - can get sick/die from HA
  • male infants: explosive neonatal HA due to abnormal gene
  • Jesse Gelsinger - first public gene therapy death

Biochem - Exam 2 (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions