a-Keto-b-Methylvaleric Acid

Of the essential amino acids, there are three branchedchain amino acids (leucine, isoleucine, and valine).

Unlike most amino acids, the initial step of branchedchain amino acid (BCAA) metabolism does not take place in the liver. They increase rapidly in systemic circulation after protein intake and are readily available for use. Skeletal muscle is where most of the initial catabolism of BCAA takes place using branched-chain aminotransferase enzymes to form α-ketoacids, which are then released from muscles back into the blood to be further metabolized, mainly in the liver.

BCAA act as substrates for protein synthesis, energy production, neurotransmitter production, glucose metabolism, immune response, and many other beneficial metabolic processes.

α-Ketoisovaleric Acid (AKIV) is produced from the essential amino acid valine. It then metabolizes to become succinyl Co-A. AKIV is glucogenic.

α-Ketoisocaproic Acid (AKIC) is produced from leucine and further metabolizes to form acetyl-CoA and acetoacetate. AKIC is ketogenic.

α-Keto-β-Methylvaleric Acid (AKBM) comes from isoleucine, and further metabolizes to form acetylCoA and succinyl-CoA. AKBM is therefore both glycogenic and ketogenic.

These α-ketoacids then require an enzyme complex called branched-chain α-keto acid dehydrogenase (BCKD) for further metabolism.

This enzyme complex requires multiple vitamin cofactors, such as vitamin B1, B2, B3, B5, and lipoic acid.

References:

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- Shibata K, Nakata C, Fukuwatari T. High-performance liquid chromatographic method for profiling 2-oxo acids in urine and its application in evaluating vitamin status in rats. Biosci Biotechnol Biochem. 2016;80(2):304-312.

- Danner DJ, Davidson ED, Elsas LJ. Thiamine increases the specific activity of human liver branched chain α-ketoacid dehydrogenase. Nature. 1975;254(5500):529-530.

- Shibata K, Sakamoto M. Urinary branched-chain 2-oxo acids as a biomarker for function of B-group vitamins in humans. J Nutr Sci Vitaminol. 2016;62(4):220-228.

- Adams SH. Emerging Perspectives on Essential Amino Acid Metabolism in Obesity and the Insulin-Resistant State. Adv Nutr. 2011;2(6):445-456.

- Shibata K, Nakata C, Fukuwatari T. High-performance liquid chromatographic method for profiling 2-oxo acids in urine and its application in evaluating vitamin status in rats. Biosci Biotechnol Biochem. 2016;80(2):304-312.

- Solmonson A, DeBerardinis RJ. Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem. 2018;293(20):7522- 7530.