(L6) Protein and AA Metabolism

Question 1

How are AAs supplied to and depleted from the body supply of AAs?

L6 S7 LO1

Answer 1

Supply:

• degradation of protein
• dietary
• synthesis of AAs

Depletion:

• production of proteins
• synthesis of nitrogen compounds
• degradation of AAs

Question 2

What is Hartnup disease?

L6 S7 LO1.a

Answer 2

Autosomal recessive defect in transporter for nonpolar/neutral AAs

Transporter found in the kidney and SI

Question 3

How does Hartnup disease present?

L6 S7 LO1.a

Answer 3

Manifest as an infant

-failure to thrive

• nystagmus
• tremor
• ataxia (intermittent)

-photosensitivity

Question 4

What is cystinuria?

L6 S7 LO1.a

Answer 4

Autosomal recessive defect in transporter for dimeric cystine and dibasic AAs

resluts in cystine cyrstals in kindeys which form renal calculi

Question 5

How does cystinuria present?

L6 S7 LO1.a

Answer 5

Abdominal pain that comes in waves linked with formation of kidney stones, renal colic

Question 6

What are exopeptidases and endopeptidases?

L6 S12 LO1.b

Answer 6

Exopeptidase:

-cleaves peptide bond from either the C or N terminus

Endopeptidase:

-cleaves peptide bond at specific site within protein

Question 7

What are the major intracellular pathways of protein degradation?

L6 S13 LO1.c,d

Answer 7

Lysosomal/autophagy:

• non-selective
• occurs in the lysosome and requires acidic pH (~5)

Proteasomal:

• selective; requires protein to be ubiquinated
• occurs in cytoplasm by proteasome complex

Question 8

What is the extracellular pathway of protein degradation?

L6 S14 LO1.d

Answer 8

Secreted, inactive zymogens which are activated by enterokinases

Question 9

What are the different AA synthesis families?

L6 S11 LO1.f

Answer 9

• Pyruvate
• Glutamate
• Aspartate
• Serine
• Aromatic

Question 10

What is the difference between ketogenic and glucogenic amino acids?

L6 S17 LO2.a

Answer 10

Ketogenic:

-can be converted into precursors for keto acids, ketones, or FAs (eg. acetyl CoA and acetoacetate)

Glucogenic:

-can be converted into precursors for gluconeogenesis (eg. pyruvate or TCA intermediates)

Question 11

What are the ketogenic only amino acids?

L6 S17 LO2.a

Answer 11

• Leucine
• Lysine

Question 12

What amino acids are both ketogenic and glucogenic?

L6 S17 LO2.a

Answer 12

• Isoleucine
• Phenylalanine
• Tryptophan
• Tyrosine
• Threonine

I Pee 3 Times

Question 13

What is the reaction catalyzed by ALT?

L6 S21-22 LO2

Answer 13

Alanine aminotransferase

Pyruvate + Glutamate -> Alanine + α-ketoglutarate

Uses PLP (vitamin B₆)

Question 14

What is the reaction catalyzed by AST?

L6 S21-22 LO2

Answer 14

Aspartate aminotransferase

OAA + Glutamate -> Aspartate + α-ketoglutarate

Uses PLP (vitamin B6)

Question 15

What is the reaction catalyzed by GA?

What is the significance of this?

L6 S21;23 LO2

Answer 15

Glutamine aminohydrolase

Glutamine + H20 -> Glutamate + NH3

Used to sequester free nitrogen in the brain.

Question 16

What is hyperhomocysteinemia?

L6 S26 LO2

Answer 16

Results from deficiencies in cofactors (B₆, B₁₂, folic acid) or enzymes (cytationine β-synthase) that cause build up of homocysteine

Risk factor for ASHD, stroke, Alzheimer’s, lens dislocation, osteoporosis, and MR

Question 17

What is maple syrup urine disease?

L6 S28 LO2

Answer 17

Autosomal recessive disease resulting from deficiency of branched-chain

α-keto acid dehydrogenase (BCKD) which is responsible for degrading branched chain AAs (isoleucine, leucine, and valine).

High concentrations of these AAs in the urine give it a smell simialr to maple syrup.

Treatment is limiting intake of these AAs.

Question 18

What is the mechanism of phenylketonuria and how is it treated?

L6 S29 LO2

Answer 18

Defect in phenylalanine hydroxylase (PAH) which converts Phe into Tyr

Phenyllactate and phenylacetate are instead produced which block AA transport into brain and prevent myelin formation.

Treatment in limitation of Phe consumption with supplementation of Tyr

Question 19

What are notable tryptophan derivatives?

L6 S34 LO3

Answer 19

Niacin

• requires B6
• used in NAD+/NADP+

5-hydroxytryptophan

• requires B6
• used in serotonin which is also used in melatonin

Question 20

What are notable tyrosine derivatives?

What diseases are realized to tyrosine derivatives?

L6 S35 LO3

Answer 20

T3 and T4

-Graves’ disease and hyper/hypothyroidism

Melaninin:

-Albinism

Dopamine:

-Parkinson’s

Norepinephrine/epinephrine

Question 21

What are notable arginine derivatives?

L6 S36 LO3

Answer 21

Creatine, creatine phosphate, and creatinine

Question 22

How is ammonia removed from the brain?

L6 S40 LO4

Answer 22

α-ketoglutarate is aminiated to glutamate and glutamate is aminated to glutamine

Glutamine in shuttled to liver

Question 23

How is ammonia removed from muscle?

L6 S41 LO4

Answer 23

Alanine is aminiated using ALT Alanine is shuttled to liver

Question 24

What is the mechanism of ammonia toxicity?

L6 S45 LO4

Answer 24

Ammonia is able to cross cell membranes as it is uncharged (unlike ammonium)

This causes a pH imbalance, most notably in astrocytes in the brain resulting in:

• cerebral edema
• intracranial hypertension

TCA cycle is also disrupted due to depletion of α-ketoglutarate

Question 25

What is the rate limiting step of the urea cycle?

Where does this occur?

L6 S43 LO4

Answer 25

Carbamoyl phosphate synthetase (in the mitochondria of the liver)

uses ammonium, bicarbonate, and ATP to form carbamoyl phosphate

Question 26

What are the molecular components that provide the atoms for urea?

L6 S42 LO4.c

Answer 26

• Bicarbonate (mitochondira)
• Ammonium ion (mitochondira)
• Water (cytoplasm)
• Aspartate (cytoplasm)