Amino Acid Catabolism (L5&6)

Question 1

What AA’s are cleaved by:

1. Pepsin
2. Trypsin
3. Chymotrypsin

Answer 1

1. C side of aromatic and acidic residues (W Y F)
2. Carboxyl side of K or R
3. C side of W Y F

Question 2

Transamination undergoes what general rxn?

What about regeneration of αKG?

Answer 2

AA + αKG → α-keto acid + Glutamate [aminotransferase (AKA transaminase)]

Glu + NAD⁺ → αKG + NH₄⁺ + NADH [Glu DH]

Question 3

What do Glutamine Synthetase and GLutaminase do?

Answer 3

Glutamine synthetase converts excess ammonia to glutamine in extrahepatic tissues where AA’s are being degraded;

Ammonia then travels in the form of Gln to tissues (liver, kidneys, small bowel (for transport to liver for urea formation))where it is released as free NH₄⁺ by glutaminase.

Question 4

What is the net rxn for the urea cycle?

What are the products for the urea cycle?

Answer 4

NH₃ + CO₂ + Asp → Urea + 2ADP+AMP+4P_i

Ornithine→Citruline→Argininosuccinate→Arg→Ornithine

NOTE: located in the liver in cytosol (except O→C in mitochondria)

Question 5

How can one diagnose a Urea Cycle disorder?

Answer 5

Respiratory alkalosis, and hyperammonemia are usually clinical features present the first day of life and are progressive

Question 6

What is the most common Urea Cycle Disorder (UCD)?

Answer 6

Ornithine transcarbamoylase (OTC) deficiency is the most common UCD and is an X-linked recessive disease. It causes dec. lvls of citrulline and inc. levels of orotate and carbamoyl phosphate (CAP).

Question 7

What are 2 chemical compounds used to treat UCD?

Answer 7

Use of sodium benzoate which will become Hippuric acid,

Use of phenylacetate which will become Phenylacetylglutamine.

Both products go to renal secretion. This can help reduce ammonia concentrations in the body.

Question 8

Which 4 AA’s can be converted directly to intermediates of the glycolytic pathway or the TCA cycle?

Answer 8

1. Gln→Glu→αKG
2. Asn→Asp→OAA
3. Ala→Pyruvate
4. Ser→Pyruvate

Question 9

What is the basice 3-step process to metabolize AA’s?

Answer 9

1. Transfer the ammonium (transamination)
2. Form a CoA derivative (Oxidative decarboxylation)
3. Oxidize to generate products

Question 10

What is maple syrup urine disease?

Answer 10

A genetic defect resulting in a deficiency in branched-chain α-keto acid DH.

You get a build up of the branched AA and their α-keto acid analogs which will appear in urine, giving it a maple syrup smell.

It’s detected in infancy thru mass spec of urine

Question 11

What does 3-hydroxy-3-methylbutyric acid (HMB) do?

Answer 11

Promotes exercise performance, muscular hypertrophy.

Used for diseases that have clinical muscle wasting (AIDS, Lou Gehrig’s disease, cancer)

Question 12

In what pathway is Vitamin B12 important for AA catabolism?

Answer 12

VMIT AA’s become propionyl-CoA which w/ cofactor biotin → Methyl malonyl CoA (D) → Methyl Malonyl CoA (L) which uses B12 and mutase → succinyl CoA.

NOTE: Biotin step can be blocked, leading to excess propionyl CoA, and mutase step can be block (via inhibiting mutase or limiting amount of B12) leading to excess reactants.

Excess materials excreted thru urine.

Question 13

Vitamin B12 looks a lot like Heme.

What is Vitamin B12’s metal cofactor?

How many coordinate bonds forms w/ it?

Answer 13

Cobalt; 6

Question 14

What is the first step in phenylalanine metabolism?

Be elaborate

Answer 14

Conversion of Phe+O₂→Tyr+H₂O [Phe hydroxylase]

Tetrahydrobiopterin (H₄-Biopterin) becomes Dihydrobiopterin (H₂-Biopterin) in this rxn. TetraHB must be regenerated using Dihydropteridine reductase (DHPR) which oxidizes NADH→NAD⁺

Question 15

In phenylketonuria (PKU), what accumulates and what pathway defects can cause this genetic disease?

How is PKU diagonsed?

Answer 15

Phe and Phenylpyruvate will accumulate.

PKU can have a defect in Phe Hydroxylase, DHPR, and/or biopterin synthesis pathway.

PKU is diagnosed by Mass Spec of serum AA’s Phe and Tyr

Question 16

Degradation of Tyr results in ___&___.

What metabolic defects occur in the genetic diseases:

1. Alkaptonuria (they pee black)
2. Hypertyrosinemia

Answer 16

Acetoacetate & Fumarate;

1. Alkaptonuria: defect in homogentistic oxidase
2. Hypertyrosinemia: defect in
   1) Tyr aminotransferase
   2) 4-hydroxyphenylpyruvate dioxygenase
   3) fumaroylacetoacetate hydrolase

Question 17

1. ___ is the major site of AA degradation and the primary site for conversion of __ to __.
2. __ is a major site for degradation of branched-chain AA’s.
3. In __ tissue (including muscle), the major products of N-containing products are __ and __ which carry the N to __ for conversion to __.

Answer 17

1. Liver is the major site of AA degradation and the primary site for conversion of ammonia to urea.
2. Muscle is a major site for degradation of branched-chain AA’s.
3. In extrahepatic tissue (including muscle), the major products of N-containing products are glutamine and alanine which carry the N to liver for conversion to urea.