alphaketoisocaproate

Alphaketoisocaproate, also known as α-ketoisocaproic acid or KIC, is an α-keto acid that represents the transamination product of the essential amino acid leucine. It is the α-keto analogue of leucine, with the amino group removed and a keto group at the α-position (systematic name 2-oxo-4-methylpentanoate).

Biochemically, KIC is formed from leucine by branched-chain amino acid transaminases (BCAT), in which leucine transfers its amino group to α-ketoglutarate to yield KIC and glutamate. KIC can be further metabolized by the branched-chain α-keto acid dehydrogenase complex, decarboxylating to form isovaleryl-CoA, a step that feeds into pathways producing acetyl-CoA and acetoacetate. The process is part of the overall catabolism of the branched-chain amino acids leucine, isoleucine, and valine. KIC is interconvertible with leucine through reversible transamination.

Clinical significance, diagnostics, and physiology: In humans, disruptions of branched-chain amino acid metabolism, such as deficiencies in the branched-chain α-keto acid dehydrogenase complex, lead to maple syrup urine disease (MSUD). In MSUD, elevated levels of leucine and its related α-keto acids, including KIC, can be detected in blood and urine and aid in diagnosis and monitoring. Leucine is considered ketogenic, and its metabolic fate through KIC ultimately contributes to acetyl-CoA and acetoacetate production. KIC also serves as a metabolic intermediate in studies of amino acid metabolism and energy production.