L36: Metabolic Processes Of Renal Cortex And Medulla

Question 1

Use of glutamine in kidney

Answer 1

1. Uptake of glutamine by kidney depends on the need to excrete H+
   - Glutamine —(glutaminase)—> Glutamate + NH3 (excrete with H) + Bicarbonate (reabsorbed)
   - Glutamate —(glutamate dehydrogenase)—> α-ketoglutarate —> TCA cycle
2. Fuel
   - Fuel in normal fed state, greater extent during fasting and metabolic acidosis
   - α-ketoglutarate fed into TCA cycle to generate energy —> OAA
   - since medullary blood flow < cortical blood flow —> juxtamedullary nephron: glucose —> pyruvate —> lactate, lactate is subsequently converted back to pyruvate in cortical nephron —> Acetyl Co-A —> TCA cycle
3. Source of new C in gluconeogenesis
   - Glutamine —> α-ketoglutarate —> OAA —> converted into Malate + Aspartate —> transported out of mitochondria —> Phosphoenolpyruvate —> gluconeogenesis

Question 2

Formation of glutamine from BCAA

Answer 2

Glutamine can be formed from NH2 group of BCAA
- Isoleucine, Leucine and Valine
—> α-ketoacid
—> TCA cycle
—> α-ketoglutarate —> glutamate —> glutamine

Question 3

One carbon metabolism enzyme and cofactors

Answer 3

Methionine synthase:

• Homocysteine —> Methionine
• Methionine cycle
• Vitamin B12 cofactor

Tetrahydrofolate reductase:

• 5,10-methylenetetrahydrofolate —> 5-methyltetrahydrofolate
• a cosubstrate for homocysteine remethylation to methionine
• folate cycle
• Vitamin B9 cofactor

Cystathionine synthase: Homocysteine —> Cystathionine

• transsulfuration pathway
• Vitamin B6 cofactor

Question 4

Inborn errors of amino acid metabolism

Answer 4

1. Maple syrup urine disease:
   - accumulation of α-keto acids of branched chain amino acid
   - Valine, Isoleucine, Leucine (most abundant, give rise to maple syrup odour)
2. Phenylketouria:
   - Phenylalanine —X—> Tyrosine
   - deficiency in Phenylalanine hydroxylase
   - Phenylalanine —> Phenylacetate (musty odour of urine) + Phenyllactate
   - Treatment: Tetrahydrobiopterin tablet (cofactors for phenylalanine hydroxylase)
3. Tyrosinemia I and II:
   - Tyrosine —X—> Fumarylacetoacetate —X—> Fumarate + Acetoacetate
4. Homocysteinemia: defect in:
   - Methionine synthase: Homocysteine —X—> Methionine (Methionine cycle, Vitamin B12 cofactor)
   - Tetrahydrofolate reductase: 5,10-methylenetetrahydrofolate —X—> 5-methyltetrahydrofolate (a cosubstrate for homocysteine remethylation to methionine, folate cycle, Vitamin B9 cofactor)
   - Cystathionine synthase: Homocysteine —X—> Cystathionine (transsulfuration pathway, Vitamin B6 cofactor)
   - effect: homocysteine x2 —> homocystine (excreted in urine)