Biochemistry of BCKD activity

The 3 amino acids valine, leucine and isoleucine are catabolized in many steps. 

First Step

Transamination using a single BCAA aminotransferase, with  α-ketoglutarate as the amine acceptor

As a result, 3 different α-keto acids are produced.

Second Step

These α-keto acids are oxidised using a common BCKD, yielding the 3 different CoA derivatives.

Isovaleryl-CoA is produced from leucine by these two reactions, alpha-methylbutyryl-CoA from isoleucine, and isobutyryl-CoA from valine.

 These acyl-CoA’s undergo dehydrogenation, catalyzed by three different but related enzymes, and the breakdown pathways then diverge.  

Leucine is ultimately converted to acetyl-CoA and acetoacetate; 

Isoleucine to acetyl-CoA and succinyl-CoA; and 

Valine to propionyl-CoA (and subsequently succinyl-CoA)

The final products of the catabolism of the 3 amino acids are fully oxidised via the TCA cycle.

So what happens when there is no BCKD or when there is dysfunctional BCKD?

The  α-keto acids will not be oxidised, causing incomplete catabolism of these amino acids. The final products acetyl-CoA and Succinyl-CoA will not be produced. This will disrupt the TCA cycle, creating less ATP and NADH for muscle.

Due to the incomplete catabolism of the animo acids, there will be a accumulation of Leucine, Isoleucine and Valine in the body.

Excessive levels of these amino acids in the body will lead to brain damage. 

References

The Alchemist Kitten (2009, November 19). The Citric Acid Cycle (aka, Krebs or TCA cycle). The Alchemist Kitten's Notebook. Retrieved June 18, 2012, from http://thealchemistkitten.wordpress.com/tag/tca-cycle/
Valine, Leucine and Isoleucine Degradation. (n.d.). Retrieved June 18, 2012, from http://pathman.smpdb.ca/pathways/SMP00032/pathway?level=2