ALPHA-KETOISOCAPROATE DIOXYGENASE - THE STEREOCHEMICAL COURSE OF THE HYDROXYLATION REACTION

a-Ketoisocaproate (KIC) dioxygenase catalyzes the oxidation of a-ketoisocaproate (1) to β-hydroxyisovalerate (2) in mammals.1This cytosolic enzyme is not generally considered to be part of the “normal” pathway for the degradation of branched-chain a-keto acids, but it has beer suggested to function as a “safety valve” to prevent the accumulation of the toxic keto acid 1, which is produced by the transamination of leucine.1 The enzyme has been highly purified from rat liver,1and 180-labeling experiments have shown that it is indeed a dioxygenase.2Both the C-3 hydroxyl group and one of the carboxyl oxygens of product 2 are derived at least in part from molecular oxygen; labeling of the carboxyl is nearly complete, bul more than half of the product molecules contain no label in the hydroxyl group2. © 1990, American Chemical Society. All rights reserved.