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T1 - Phase 1 - Integrated (II) > Pulm/Renal - Biochemistry - Amino Acid Metabolism: Inborn Errors of Metabolism, Porphyrias, Jaundice > Flashcards

Pulm/Renal - Biochemistry - Amino Acid Metabolism: Inborn Errors of Metabolism, Porphyrias, Jaundice Flashcards

1
Q

Amino acids whose citric acid cycle intermediates can be subsequently converted to ____________ are termed glucogenic as they are easily entered into gluconeogenesis.

Amino acids whose citric acid cycle intermediates can be subsequently converted to ____________ are termed ketogenic as they are easily entered into fatty acid or ketone synthesis.

Amino acids whose citric acid cycle intermediates can be subsequently converted to ____________ are termed both glucogenic and ketogenic as they are easily entered into both of the above pathways.

A

Oxaloacetate;

acetyl-CoA;

pyruvate

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2
Q

Amino acids whose citric acid cycle intermediates can be subsequently converted to pyruvate are termed ___________.

Amino acids whose citric acid cycle intermediates can be subsequently converted to oxaloacetate are termed ___________.

Amino acids whose citric acid cycle intermediates can be subsequently converted to acetyl-CoA are termed ___________.

A

Both ketogenic and glucogenic;

glucogenic;

ketogenic

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3
Q

Which are the amino acids that are solely ketogenic (2)?

What does this mean?

A

Leucine, lysine;

they are easily converted to acetyl-CoA

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4
Q

Which are the amino acids that are solely glucogenic (9)?

What does this mean?

A

Arginine

Asparagine & Glutamine

Aspartate & Glutamate

Histidine

Methionine

Proline

Valine;

they are easily converted to oxaloacetate

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5
Q

Which are the amino acids that are either ketogenic or glucogenic (9)?

What does this mean?

A

Alanine

Cysteine

Glycine

Isoleucine

Phenylalanine

Serine

Threonine

Tryptophan

Tyrosine;

they are readily converted to pyruvate (which is easily convertible to acetyl-CoA and oxaloacetate)

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6
Q

Decide (for each AA individually) if each of the following amino acids is ketogenic, glucogenic, or both:

Proline

Tryptophan

Serine

Valine

Methionine

A

Glucogenic

Both

Both

Glucogenic

Glucogenic

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7
Q

Decide (for each AA individually) if each of the following amino acids is ketogenic, glucogenic, or both:

Threonine

Histidine

Lysine

Isoleucine

Glutamine

A

Both

Glucogenic

Ketogenic

Both

Glucogenic

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8
Q

Decide (for each AA individually) if each of the following amino acids is ketogenic, glucogenic, or both:

Glutamate

Aspartate

Phenylalanine

Asparagine

Aspartate

A

Glucogenic

Glucogenic

Both

Glucogenic

Glucogenic

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9
Q

Decide (for each AA individually) if each of the following amino acids is ketogenic, glucogenic, or both:

Arginine

Cysteine

Leucine

Tyrosine

Glycine

A

Glucogenic

Both

Ketogenic

Both

Both

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10
Q

Any amino acid that can be converted to (1) _________ is termed both glucogenic and ketogenic because (1) can be converted both to (2) _________ and (3) _________.

(Note: not all AA that are both glucogenic and ketogenic can be converted to (1). Some can enter the citric acid cycle at multiple intermediates.)

A

(1) Pyruvate,
(2) acetyl-CoA, (3) oxaloacetate

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11
Q

What are the (1) buildup product(s) and (2) deficient enzyme of homocystinuria?

A

Homocysteine (and possibly methionine);

cystathione β-synthase

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12
Q

What are the (1) buildup product(s) and (2) deficient enzyme of maple syrup urine disease?

A

Branched-chain ketoaciduria;

branched-chain α-ketoacid dehydrogenase complex

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13
Q

What are the (1) buildup product(s) and (2) deficient enzyme of methylmalonic acidemia?

A

L-Methylmalonic acid (and possibly propionyl-CoA);

methylmalonyl-CoA mutase

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14
Q

What are the (1) buildup product(s) and (2) deficient enzyme of phenylketonuria?

A

Phenylalanine;

phenylalanine hydroxylase

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15
Q

What are the (1) buildup product(s) and (2) deficient enzyme of alkaptonuria?

A

Homogentisate;

homogentisate oxidase

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16
Q

What are the (1) buildup product(s) and (2) deficient enzyme of type I tyrosinemia?

A

Fumarylacetoacetate;

fumarylacetoacetate hydrolase

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17
Q

What are the (1) buildup product(s) and (2) deficient enzyme of type II tyrosinemia?

A

Tyrosine;

tyrosine aminotransferase

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18
Q

What inborn error of metabolism is associated with a buildup of homocysteine (and possibly methionine)?

What enzyme is deficient?

A

Homocystinuria;

cystathione β-synthase

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19
Q

What inborn error of metabolism is associated with a buildup of branched-chain α-ketoacids?

What enzyme is deficient?

A

Maple syrup urine disease;

branched-chain α-ketoacid dehydrogenase complex

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20
Q

What inborn error of metabolism is associated with a buildup of L-methylmalonic acid?

What enzyme is deficient?

A

Methylmalonic acidemia;

methylmalonyl-CoA mutase

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21
Q

What inborn error of metabolism is associated with a buildup of phenylalanine?

What enzyme is deficient?

A

Phenylketonuria;

phenylalanine hydroxylase

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22
Q

What inborn error of metabolism is associated with a buildup of homogentisate?

What enzyme is deficient?

A

Alkaptonuria;

homogentisate oxidase

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23
Q

What inborn error of metabolism is associated with a buildup of fumarylacetoacetate?

What enzyme is deficient?

A

Type I tyrosinemia;

fumarylacetoacetate hydrolase

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24
Q

What inborn error of metabolism is associated with a buildup of tyrosine?

What enzyme is deficient?

A

Type II tyrosinemia;

tyrosine aminotransferase

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25
Q

Phenylketonuria is basically an inability to convert ____________ to ___________.

Why does this affect neurotransmitter production?

A

Phenylalanine, tyrosine;

tyrosine is a precursor for catecholamine synthesis

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26
Q

Asides from a phenylalanine hydroxylase deficiency (the most common cause), what other issues might cause phenylketonuria?

A

(1) A deficiency of tetrahydrobiopterin (BH4) (a cofactor for phenylalanine hydroxylase and catecholamine synthesis);
(2) an inability to regenerate BH4 from BH2 (via dihydropteridine reductase)

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27
Q

A 45-year-old male presents with complaints of worsening arthralgias. Upon further studies, you note that his urine turns brown when left exposed to air.

What is at the top of your differential?

What deficiency is responsible?

A

Alkaptonuria;

the enzyme homogentisate oxidase

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28
Q

How is maple syrup urine disease managed?

A

Via restriction of branched-chain amino acids

(valine, isoleucine, leucine)

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29
Q

What substrate may build up in cases of severe B12 deficiency, causing acidemia?

This is because a certain enzyme involving acids requires B12 as a cofactor. Which is it?

This is an alternate cause of what type of acidemia?

A

L-Methylmalonic acid;

methylmalonyl-CoA mutase;

methylmalonic acidemia

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30
Q

What are the two major methyl donors in the body?

A

S-Adenosylmethionine;

folate (and its derivatives)

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31
Q

What two vitamins are needed for S-adenosylmethionine (SAM) (a methyl donor) regeneration?

After donating its methyl group, SAM becomes S-adenosylhomocysteine, then homocysteine, then methionine.

In which part of this chain are the two vitamins necessary?

A

B12 and folate;

the conversion of homocysteine to methionine

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32
Q

After donating its methyl group, S-adenosylmethionine (SAM) becomes S-adenosylhomocysteine, then homocysteine.

What are the two products that are typically now produced from homocysteine?

Which vitamins are required for each path?

A

Either: (1) methionine (to regenerate SAM), B12 and folate;

or (2) cystathione, B6 (pyridoxal phosphate)

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33
Q

Methylmalonyl-CoA can be created from the metabolism of propionyl-CoA. It is then often converted to _____________ to enter the citric acid cycle.

What enzyme and vitamin are involved in this conversion?

A

Succinyl-CoA;

methylmalonyl-CoA mutase, B12

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34
Q

A deficiency of which of the following can cause an elevation in blood homocysteine: vitamin B12, vitamin B6, or folate?

A deficiency of which of the following can cause an elevation in blood L-methylmalonic acid: vitamin B12, vitamin B6, or folate?

A

All three;

B12 only

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35
Q

What acid often builds up in addition to L-methylmalonic acid?

A

Propionic acid

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36
Q

If poorly controlled, which of the following inborn errors of metabolism are most likely to cause intellectual disability and other neurological disabilties?

Alkaptonuria

Type I tyrosinemia

Type II tyrosinemia

Phenylketonuria

Homocystinuria

Maple syrup urine disease

Methylmalonic acidemia

A

Type II tyrosinemia

Phenylketonuria

Homocystinuria

Maple syrup urine disease

Methylmalonic acidemia

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37
Q

How does type I tyrosinemia often present?

A

A cabbage-like odor in the urine;

liver failure, renal tubular acidosis

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38
Q

Which are the *conditionally essential amino acids (6)?

(*E.g. essential during growth, pregnancy, illness, etc.)

A

Arginine

Cysteine

Glutamine

Glycine

Proline

Tyrosine

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39
Q

Which are the nonessential amino acids (5)?

A

Alanine

Asparagine

Aspartate

Glutamate

Serine

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40
Q

State if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Alanine

A

Nonessential;

both;

pyruvate

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41
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Arginine

A

Conditionally essential;

glucogenic;

α-ketoglutarate

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42
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Asparagine

A

Nonessential;

glucogenic;

oxaloacetate

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43
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Aspartate

A

Nonessential;

glucogenic;

oxaloacetate

44
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Cysteine

A

Conditionally essential

both;

pyruvate

45
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Glutamine

A

Conditionally essential;

glucogenic;

α-ketoglutarate

46
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Glutamate

A

Nonessential;

glucogenic;

α-ketoglutarate

47
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Glycine

A

Conditionally essential;

both;

pyruvate

48
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Histidine

A

Essential;

glucogenic;

α-ketoglutarate

49
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Isoleucine

A

Essential;

both;

succinyl-CoA, acetyl-CoA

50
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Leucine

A

Essential;

ketogenic;

acetyl-CoA, acetoacetate

51
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Lysine

A

Essential;

ketogenic;

acetoacetate

52
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Methionine

A

Essential;

glucogenic;

succinyl-CoA

53
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Phenylalanine

A

Essential;

both;

fumarate, acetoacetate

54
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Proline

A

Conditionally essential;

glucogenic;

α-ketoglutarate

55
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Serine

A

Nonessential

both;

pyruvate

56
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Threonine

A

Essential;

both;

succinyl-CoA. acetyl-CoA

57
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Tryptophan

A

Essential;

both;

pyruvate, acetoacetate, acetyl-CoA

58
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Tyrosine

A

Conditionally essential;

both;

fumarate, acetoacetate

59
Q

First, state if the following amino acid is essential, conditionally essential, or nonessential.

Second, state if the following amino acid is glucogenic, ketogenic, or both.

Third, name the citric acid cycle intermediate(s) into which it is readily convertible.

Valine

A

Essential;

glucogenic;

succinyl-CoA

60
Q

What enzyme can convert aspartate and α-ketoglutarate to oxaloacetate and glutamate?

What enzyme can interconvert glutamate and α-ketoglutarate?

A

Aspartate aminotransferase (AST);

glutamate dehydrogenase

61
Q

What enzyme can convert glutamate to glutamine?

What enzyme can convert glutamine to glutamate?

A

Glutamine synthetase;

glutaminase

62
Q

What enzyme can interconvert alanine and pyruvate?

What enzyme can interconvert aspartate and oxaloacetate?

A

Alanine aminotransferase (ALT);

aspartate aminotransferase (AST)

63
Q

What enzyme can convert aspartate to asparagine?

What enzyme can convert asparagine to aspartate?

A

Asparagine synthetase;

asparaginase

64
Q

In the Cahill cycle, what molecule travels from the muscle to the liver to boost gluconeogenesis?

In the Cori cycle, what molecule travels from the muscle to the liver boost gluconeogenesis?

A

Alanine;

lactate

65
Q

The Cahill cycle increases liver gluconeogenesis in times of ____________.

The Cori cycle increases liver gluconeogenesis in times of ____________.

A

Starvation;

hypoxia

66
Q

Epinephrine, norepinephrine, and dopamine are synthesized from what common precursor?

A

Tyrosine

67
Q

Starting with tyrosine, what is the order of intermediates and products in catecholamine synthesis?

A

Tyrosine –>

DOPA –> Dopamine –> Norepinephrine –> Epinephrine

68
Q

GABA is made from what immediate precursor?

Histamine is made from what immediate precursor?

Serotonin is made from what precursors?

A

Glutamate;

histidine;

tryptophan, then 5-HT

69
Q

Which neurotransmitters require pyridoxal phosphate (B6 derivative) for their synthesis?

A

Dopamine (from DOPA);

GABA (from glutamate);

histamine (from histidine);

serotonin (from 5-HT)

70
Q

What cofactors are needed for the synthesis of DOPA from tyrosine?

What cofactors are needed for the synthesis of epinephrine from norepinephrine?

What cofactors are needed for the synthesis of norepinephrine from dopamine?

A

Tetrahydrobiopterin (BH4; aka Kuvan);

vitamin C and copper (Cu2+);

vitamin B12, folate, S-adenosylmethionine

71
Q

Why are Parkinsons patients treated with both L-DOPA and carbidopa?

(Hint: L-DOPA stimulates dopamine production in both the CNS and PNS.)

A

Carbidopa inhibits PNS dopamine production, limiting the L-DOPA-driven increase in dopamine production to just the CNS

72
Q

What are porphyrias?

A

Rare disorders of heme synthesis

73
Q

Which is the most common porphryia?

A

Cutanea tarda

74
Q

Which porphryia does not cause a sensitivity to light?

A

Acute intermittent porphyria

75
Q

Which porphyrias are hepatic?

A

Cutanea tarda (both erythropoeitic and hepatic);

acute intermittent;

hereditary coproporphyria;

variegate

76
Q

Which substrate sometimes produced in porphyrias can produced skin photosensitivity?

A

Uroporphyinogen I

77
Q

Which porphyrias are erythropoeitic?

A

Cutanea tarda (both erythropoeitic and hepatic);

congenital erythropoeitic;

erythpoeitic protoporphyria

78
Q

Name the enzyme defect and buildup product for the following porphyria:

Acute intermittent porphyria

A

Hydroxymethylbilane synthetase;

porphobilinogen & δ-ALA

79
Q

Name the enzyme defect and buildup product for the following porphyria:

Congenital erythropoeitic porphyria

A

Uroporphyrinogen III synthase;

uroporphyrinogen I & coproporphyrinogen I

80
Q

Name the enzyme defect and buildup product for the following porphyria:

Cutanea tarda porphyria

A

Uroporphyrinogen decarboxylase;

uroporphyrin

81
Q

Name the enzyme defect and buildup product for the following porphyria:

Hereditary coproporphyria

A

Coproporphyrinogen oxidase;

coproporphyrinogen III

82
Q

Name the enzyme defect and buildup product for the following porphyria:

Variegate porphyria

A

Protoporphyrinogen oxidase;

protoporphyrinogen IX

83
Q

Name the enzyme defect and buildup product for the following porphyria:

Erythropoeitic protoporphyria

A

Ferrochetalase;

protoporphyrin

84
Q

What is the rate-limiting step of heme synthesis?

A

ALA synthase forms δ-ALA

85
Q

Which steps of heme synthesis are inhibited by lead poisoning?

(Which enzymes are involved?)

A

The 2nd step and the final step

(ALA dehydratase & ferrochetalase)

86
Q

Describe the functions of the spleen and the liver in bilirubin metabolism.

A

1. Splenic macrophages destroy senescent erythrocytes, releasing bilirubin

2. Unconjugated bilirubin is carried to the liver by albumin

3. The liver conjugates the bilirubin with glucuronic acid

87
Q

After the spleen destroys senescent RBCs, bilirubin forms, and the liver conjugates that bilirubin with ________________,

what happens next (as far as elimination of the bilirubin from the body)?

A

Glucuronic acid;

1. The conjugated bilirubin is secreted into the duodenem in bile

2. The intestinal flora deconjugates the bilirubin and converts it to urobilinogen

3. This urobilinogen either remains in the gut and is secreted in feces as stercobilin or reabsorbed and secreted in the urine as urobilin

88
Q

The liver enzyme ___________ ___________ conjugates bilirubin with __________ __________ to form __________ __________ (conjugated bilirubin).

A

Bilirubin glucuronyltransferase;

glucuronic acid;

bilirubin diglucuronide

89
Q

What form of bilirubin is most elevated in the blood in cases of hemolytic jaundice?

A

Unconjugated

90
Q

What form of bilirubin is most elevated in the blood in cases of obstructive jaundice?

A

Bilirubin diglucuronide (conjugated bilirubin)

91
Q

What form of bilirubin is most elevated in the blood in cases of hepatocellular jaundice?

A

Both unconjugated bilirubin and conjugated (bilirubin diglucuronide)

92
Q

Why do some newborns develop neonatal jaundice?

Is this a problem?

A

Their hepatic bilirubin glucuronyltransferase (the conjugating enzyme) is not yet fully functional;

yes, it can cause kernicterus (neonatal jaundice-induced encephalopathy)

93
Q

Why is unconjugated bilirubin called indirect bilirubin?

Why is conjugated bilirubin called direct bilirubin?

A

It does not react as easily with reagent and is determined by ‘total bilirubin - direct bilirubin;’

it reacts easily with reagent and is directly measured

94
Q

__________ __________ is an energy carrier in the muscle formed by the phosphorylation of __________.

Both of the above molecules can cyclize to form __________, which is quickly secreted by the kidneys.

A

Creatine phosphate, creatine;

creatinine

95
Q

Decreased levels of plasma creatinine are indicative of:

Elevated levels of plasma creatinine are indicative of:

Elevated levels of creatine kinase are indicative of:

A

Muscle atrophy;

kidney dysfunction;

possible myocardial infarction

96
Q

What enzyme turns muscle creatine into creatine phosphate?

A

Creatine kinase

97
Q
A

A.

98
Q
A

A.

99
Q
A

D.

100
Q
A

A.

101
Q
A

E.

102
Q
A

E.

103
Q
A

A.

104
Q
A

A.

105
Q
A

B.

106
Q
A

D.

T1 - Phase 1 - Integrated (II) (23 decks)

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