Branched chain amino acids include leucine, isoleucine, and valine. They are broken down by the branched chain alpha-ketoacid dehydrogenase complex in mitochondria. A defect in this enzyme can cause branched chain ketoaciduria, where patients accumulate branched chain amino acids and their keto acids in their urine, which smells like maple syrup or burnt sugar. This rare genetic disorder impairs other amino acid transport and protein synthesis, and can lead to seizures, vomiting, ketoacidosis, coma, and death if not treated with a low-branched chain amino acid diet and thiamine supplementation.

2. Branched Chain Amino Acids

3. Branched
chain
Essential
amino acid
Aliphatic side
chain (3C)
.

4. Branched
chain
Essential
amino acid
Aliphatic side
chain (4C)
.

5. Branched
chain
Essential
amino acid
Aliphatic side
chain (4C)
.

6.  Based on the products obtained from the carbon
skeleton, the branched chain amino acids are
either…

7. Valine
α-ketoisovalerate
Isoleucine Leucine
α-keto-β-
methylvalerate
α-ketoisocaproate
Isobutyryl CoA 2-methylbutyryl CoA Isovaleryl CoA
Methylacrylyl-CoA Triglyl CoA
β-methylcrotonyl
CoA
HMG CoA
Acetoacetate
Propionyl CoA
Acetyl CoA
T r a n s a m i n a t i o n T r a n s a m i n a t i o n
Methylmalonyl CoA
α - K e t o a c i d D e h y d r o g e n a s e
Biotin
Propionyl CoA
Methylmalonyl CoA
Glucose Fat
CO2
CO2
CO2
CO2
Glucose
CO2
Biotin

8. Branched chain α-ketoacid
Dehydrogenase Complex
 Mitochondrial enzyme
 Multi-enzyme complex
 Decarboxylase
 Transacylase
 Dihydrolipoyl dehydrogenase.
 Co-Enzymes -
 NAD
 Co-A
 Lipoic acid
 FAD
 TPP.

9. β-methylcrotonyl CoA
HMG CoA
Acetoacetate Acetyl CoA

10. Triglyl CoA
Methylacetoacetyl CoA
Propionyl
CoA
Acetyl CoA
Lyase

11. Methylacrylyl CoA
Propionyl CoA
Succinyl CoA
Methylmalonyl CoA
Glucose

13. The urine of the affected individuals smells like
maple syrup or burnt sugar
Other name: Branched chain Keto aciduria
Genetic: An autosomal recessive disorder.
Incidence : fewer than 1 in 1,00,000 individuals.
Enzyme defect: Branched chain α-ketoacid
dehydrogenase,
The net outcome: blockade in the conversion of α-
keto acids to the respective acyl CoA thioesters.
Leads to: Accumulation and excretion of branched
amino acids and their keto acids.

14. Accumulation of BCAAs causes an
impairment in transport & function of other
amino acids.
Protein biosynthesis is reduced.
BCAAs competitively inhibit glutamate
dehydrogenase.

15. Clinical Features –
Severe M.R,
Convulsions,
Vomiting,
Acidosis (ketoacidosis),
Coma and
Death.

16. Diagnosis-
 An early diagnosis by Enzyme Analysis.
Plasma & Urine - ↑ Leu , Ile , Val and
their α-ketoacids .
Smell of Urine – Burnt Sugar
Chromatography of Urine.
Rothera’s Test - + ve.
 Rx –
Diet low in BCA.
High in Thiamine.