Ketoisovaleric acid is an abnormal metabolite originated from the incomplete breakdown of branched-chain amino acids. Chronically high levels of ketoisovaleric acid are associated with maple syrup urine disease (MSUD). MSUD is an inherited metabolic disorder caused by deficiency of branched-chain α-keto acid dehydrogenase complex activity which leads to accumulation of the branched-chain α-keto acids including α-ketoisocaproic acid, α-ketoisovaleric acid and α-keto-β-methylvaleric acid, as well as their respective amino acids in blood and urine. From a chemistry perspective, ketoisovaleric acid is a keto acid, which is a subclass of organic acids. Abnormally high levels of organic acids in blood (organic acidemia), urine (organic aciduria), the brain, as well as other tissues result in general metabolic acidosis.

References:

1. HMDB0000019 (alpha-Ketoisovaleric acid). The Human Metabolome Database. Retrieved on September 7, 2021.

2. Bridi R, Braun CA, Zorzi GK, et al. alpha-keto acids accumulating in maple syrup urine disease stimulate lipid peroxidation and reduce antioxidant defences in cerebral cortex from young rats. Metabolic Brain Disease, 2005, 20(2): 155-167.