48-49. AA metabolism

Question 1

AA function - NT

Answer 1

Glycine - inhibitory in SC
Aspartate - excitory in SC
GABA- inhibitory in CNS
Glutamate - excitory in CNS

Question 2

AA function - precursor for monoamine NT

Answer 2

Phenylalanine–>tyrosine–>DOPA–>dopamine–>Norepinephrine.
Tryptophan–>serotonin–>melatonin.
Vit.B6 derivative pyridoxal phosphate is required cofactor.

Question 3

AA function - precursor for nitrogen-containing compounds

Answer 3

Creatine (glycine + arginine).
Aminoleuvulinic acid (succinyl CoA+glycine) is a key IM for heme

Question 4

AA function - donors of single carbon

Answer 4

Methionine (carried by SAM).

glycine, methionine, histidine and serine (carried by THF)

Question 5

AA function - enzyme regulators

Answer 5

leucine (+) for GDH.

Arginine (+) for NAGS (urea cycle)

Question 6

Kwashiokor

Answer 6

Protein malnutrition (negative nitrogen balance)
Sx: generalized edema, reddish pigment in hair, failure to grow, lethargy, irritability and poor movement. Fatty liver.

Question 7

Digestion of dietary protines

Answer 7

Stomach: acid-hydroysis and pepsin
SI: cholecystokinin stimulates release of zymogens from pancreas. Secritin stimulates bicarbonate release.
Zymogens: trysinogen is converted to trypsin by enteropeptidase. the rest of zymogen are activated by trypsin.

Question 8

AA absorption and transport

Answer 8

Enterocytes in gut lumen secret aminopeptidases which process peptides into free aa for di-/tripeptides.
ATP hydrolysis-driven active transporters transport AAs.
Na+-linked transport free AA.
H+-linked transport di/tripeptides.

Question 9

Cystinuria

Answer 9

AR disease caused by mutation in cysteine transporters.
Cysteine transporter: cysteine, ornithine, arginine and lysine –> all elevated.
Kidney stone –> reduced excretion
Fq bacterial infection, sickle-shaped crystal in urine.
TX: oral hydration and solubilization of cysteine.

Question 10

Biosynthesis of amino acids (GYPSY DANCE QUEEN)

Answer 10

1. Transamination of alpha-keto acids: Ala, Asp, Glu.
2. Addition of ammonia: Glm, Asg
3. Crystalization and reduction of Glu: proline
4. Oxi and trasamination of 3PGA: serine
5. Removal of hydroxymethy group of serine: Gly.
6. Synthesis from essential AA: cysteine and Tyro.

Question 11

Amino Acid catabolism

Answer 11

1. Transamination
2. Oxidative deamination (GDH)
3. Transport to liver
4. Excretion of ammonia
5. Carbon skeleton catabolism

Question 12

AA catabolism: 1. Transamination

Answer 12

All amino acids transfer amino groups to glutamate. Aminotransferases are aa-specific.
ALT: alanine+pyruvate = alpha-keto + glutamate
AST: aspartate+oxalo = alpha-keto +glutamate

Coenzyme: pyridoxal phosphate (Vit.B6)

Question 13

AA catabolism: 2. oxidative deamination (GDH)

Answer 13

Glutamate DH.
Glu+NAD –> alpha-keto + NH3 (forward)
alpha-keto + NADPH + NH3 –> glu + NADP

+ by ADP and leucine / - by GTP

Question 14

HI/HA: GDH mutation

Answer 14

Mutation to GTP binding site on GDH leads to hyperactive GDH.
Decreased glu, increased alpha-keto (TCA cycle) increased ammonia and increased insulin (due to increased ATP)

Question 15

AA catabolism: 3. Transport to liver

Answer 15

In most tissue, glutamine synthase combine ammonia with glutamate to form glutamine.
Glutamine is transported to liver then converted back to glutamate by glutaminase.

In muscle: GDH and ALT form alanin-glucose cycle (between muscle and liver).
glucose–>pyruvate.
pyruvate + glutamate –> alanine + alpha-keto
alanine goes to liver and converted back to glutamate.

Question 16

AA catabolism: 4. Ammonia excretion

Answer 16

ammonia is eventually converted to urea and excreted.
Urea can be used up by bacterial urease.
Kidney failure results in hyperammonemia.

In metabolic acidosis, kidney will increase NH3 production by glutaminase.
In metabolic alkalosis, kidney will decrease NH3 production.

Question 17

AA catabolism: 5. Carbon skeleton catabolism

Answer 17

Glucogenic vs. Ketogenic (leucine/lycine)

Branched amino acids (L/I/V)

Question 18

AA catabolism: 5a. glucogenic aa

Answer 18

glycine –> serine –> pyruvate
Phenyl –> tyrosine –> fumerate and acetoacetate
Asg –> Asp –> oxaloacetate
Histidine –> urocanic acid –> FIGlu –> glutamate –> alpha-keto (FIGlu–>glu uses THF)
Proline –> glutamate (using 2 NAD)
Arg –> ornithine –>–>–>glutamate

Question 19

AA catabolism: 5b. Ketogenic aa

Answer 19

leucine and lycine exclusively produce ketone bodies.

Question 20

AA catabolism: 5c. Branched amino acids

Answer 20

Leucine, isoleucine and valine are branched amino acids.
Trasamination: BCKD converts them into alpha-keto acids.
Coenzymes: NAD, FAD, CoA, lipoic acid and thiamine pyrophosphate.
BCKD has 3 subunits: decarboxylase, transacylase, and lipoamide oxidoreductase.
BCKD defect leads to maple syrup urine dz.

Dehydrogenation:
Isovaleryl CoA DH for leucine metabolite.
Short-chain fatty acyl DH for isobutylryl and methyl-butylryl CoAs –> propionyl CoA eventually.

Propionyl CoA –> methylmalonyl CoA using biotin.
Propionyl acidemia leads to urea cycle inhibited.
Methylmalonyl CoA –> succinyl CoA using VB12.

Question 21

Single Carbon Carriers: SAM

Answer 21

methionine –> SAM by SAM synthase + ATP.

Hydrolysis: SAM –> S-adenosylhomocysteine –> homocysteine.
Homocysteine has two fates.
Homocysteine –> Cystathionine –> cysteine using 2 Vit.B6
Homocysteine + N5-methyl THF –> methionine + THF

Question 22

Single carbon carriers: THF

Answer 22

Formate + THF –> 10-formyl-THF
Histidine + THF –>5,10-methenyl-THF
Glycine/serine + formaldehyde + THF –> 5,10,methenyl-THF

10-F-THF –> 5,10-M-THF –> 5,10-Mn-THF–> 5-methyl-THF (dead-end).

Only regeneration of methionine restores 5-M-THF back to THF. Needs vit.B12. (folate trap)