Branched Chain Amino Acids

Expansion

The three branched chain amino acids: leucine, isoleucine and valine. All are essential, and uniquely they are metabolised principally in skeletal muscle rather than the liver, because muscle has the transaminase and the liver largely does not.

Ketogenic versus glucogenic

• Purely ketogenic: leucine and lysine only. Remembered as “the two Ls”
• Both: isoleucine, phenylalanine, tyrosine, tryptophan
• All the rest are glucogenic

This matters because ketogenic amino acids cannot be converted to glucose, which is why they cannot support gluconeogenesis in starvation.

Maple syrup urine disease

• Autosomal recessive deficiency of branched chain alpha-ketoacid dehydrogenase
• Accumulation of the three amino acids and their ketoacids
• Presents in the neonate with poor feeding, vomiting, lethargy, hypertonia, seizures and encephalopathy
• Urine and cerumen smell of maple syrup or burnt sugar
• Detected on the UK newborn blood spot screen
• Treated with dietary restriction of the three amino acids, and thiamine in responsive variants

The enzyme uses thiamine (B1) as a cofactor, shared with pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, which is why all three are affected in thiamine deficiency.