This document summarizes the metabolism of branched chain amino acids (BCAAs) - valine, isoleucine, and leucine. It discusses that the initial reactions in BCAA catabolism are common, involving transamination, oxidative decarboxylation, and dehydrogenation to form acyl-CoA derivatives. It then explains that the subsequent catabolism of each BCAA differs and leads to the formation of acetyl-CoA and succinyl-CoA. One key point is that defects in BCAA catabolism can cause metabolic disorders like maple syrup urine disease, where the branch chain keto acid dehydrogenase enzyme is deficient.

1. Life is a succession of lessons
Which must be lived to be understood.
Metabolism
of
Branched Chain
amino acids
Dr. Dhiraj J Trivedi

2. Metabolism
of
branch chain amino acids

3. Branch chain amino acid
• Valine, Isoleucine and leucine --- Branch chain AA
• Aliphatic amino acids, Essential amino acids
• Oxidation of three amino acids are similar
• Oxidised to
• Valine to succinyl CoA – Glucogenic
• Isoleucine to Succinyl CoA and Acetyl CoA – Gluco &
Ketogenic
• Leucine to Acetyl CoA – Ketogenic (pure)

4. Initial reactions common for three AA
• A phase reactions
• 1. Reversible transamination
• 2. Oxidative decarboxylation (Similar to PA–
Acetyl CoA)
• 3. Dehydrogenation -- FAD Dependent
• B phase reactions
• Subsequent catabolism to
• Succinyl CoA and Acetyl CoA

5. Valine Isoleucine Leucine
α Keto isoValerate α keto β methyl
Valerate
α -Keto
isoscaproate
α-K G
Branch Chain amino acid transaminase
Glutamate
PLP
1. All three amino acids under go
transamination to form respective keto
acids
Muscle
Brain
Adipose

6. α Keto isoValerate
α keto β methyl
Valerate
α -Keto
isoscaproate
2. All three ketoacid than under go
Oxidative decarboxylation to form Respective acyl CoA
CO2
Isobutyryl CoA α methyl
Butyryl CoA
Iso Valeryl CoA
NAD+
CoA SH
NADH H+
TPP, FAD
Branch Chain Keto acid dehydrogenase complex
Deficiency of enzyme branch chain keto acid dehydrogenase -- MSUD

7. MSUD – maple syrup urine disease (1 :
185000)
Deficiency branch chain keto acid dehydrogenase
Types Classical – Severe deficiency
Intermittent type – Enzyme activity decreased,
Thiamine responsive – Defect stabilised by Vit B1
Clinical
Feature
Seen in child hood, does not take feed, Vommiting,
MR, Acidosis, poor muscle tone, death may after 1 yr.
Urine smells like burnt sugar.
Diagnosis Urine Dinitrophenyl hydrazine test – yellow turbidity
Treatment Restriction of Branch chain amino acids, high dose of
Thiamin

8. Isobutyryl CoA
α methyl
Butyryl CoA Iso Valeryl CoA
Methyl acrylyl CoA
Tiglyl CoA
β Methyl
Crotonyl CoA
3. Acyl CoA is further dehydrogenated in presence of FAD
FAD+
FADH2
FAD +
FADH2
Acyl CoA dehydrogenase

9. Methyl acrylyl CoA Tiglyl CoA β Methyl
Crotonyl CoA
ATP
ADP + Pi
Enoyl CoA
hydratase
4. Individual amino acids now under go separate reactions
CO2
Biotin
Carboxylase
β –OH
Isobutyryl CoA
α methyl-
β –OH butyryl CoA
β methyl
glutaconyl CoA
H2O Enoyl CoA
hydrataseH2O

10. H2O
Hydrolase
Hydratase
β –OH
Isobutyrate
α Methyl
Acetoacetyl CoA
HMG CoA
β –OH
Isobutyryl CoA
α methyl
β –OH butyryl CoA
Dehydrogenase
β methyl
glutaconyl CoA
H2O
CoASH H2
5

11. HMG CoA
lyase
β –OH
Isobutyrate
α Methyl
Acetoacetyl CoA
HMG CoA
2NAD+
2NADH + H+
CoA SH
Methyl malonate
Dehydrogenase
Ketothiolase
Acetyl CoA +
Propionyl CoA
Acetyl CoA +
Acetoacetate
6

12. CoASH
Methyl malonate
Methyl malonyl CoA
Acetyl CoA +
Propionyl CoA
Acetyl CoA +
Acetoacetate
H2O
Succinyl CoA
Vit B12
Succinyl CoA
Acetyl CoA
Acetyl CoA
Acetyl CoA
7

14. Disorders of branch chain AA
Disorder
• 1. MSUD
• 2. Isovaleric acidemia
• 3. Propionic acidemia
• 4. Methyl malonic
aciduria
Enzyme deficient
Dehydrogenase
Dehydrogenase
Carboxylase
B12 or
isomerase

16. Thank you