Dual Activities of Oxidation and Oxidative Decarboxylation by Flavoenzymes

Abstract

Specific flavoenzyme oxidases catalyze oxidative decarboxylation in addition to their classical oxidation reactions in the same active sites. The mechanisms underlying oxidative decarboxylation by these enzymes and how they control their two activities are not clearly known. This article reviews the current state of knowledge of four enzymes from the l-amino acid oxidase and l-hydroxy acid oxidase families, including l-tryptophan 2-monooxygenase, l-phenylalanine 2-oxidase and l-lysine oxidase/monooxygenase and lactate monooxygenase which catalyze substrate oxidation and oxidative decarboxylation. Apart from specific interactions to allow substrate oxidation by the flavin cofactor, specific binding of oxidized product in the active sites appears to be important for enabling subsequent decarboxylation by these enzymes. Based on recent findings of l-lysine oxidase/monooxygenase, we propose that nucleophilic attack of H2 O2 on the imino acid product is the mechanism enabling oxidative decarboxylation.