Physiological aspects and mechanism of action of mevalonate 5-diphosphate decarboxylase

1. This work reviews the present knowledge of the physiological role and mechanism of action of mevalonate 5-diphosphate decarboxylase, the third enzyme involved in the biosynthesis of cholesterol from mevalonic acid. 2. Published evidence indicates that this and other enzymes of the cholesterol biosynthetic pathway present coordinate fluctuations in activity in rat liver. A possible regulatory role for the brain decarboxylases from chicken and rat has been proposed. 3. From kinetic and stereochemical studies with the chicken liver enzyme it has been proposed that the reaction is initiated by the abstraction of a proton from the 3-hydroxyl group of mevalonate 5-diphosphate by a basic group in the enzyme, followed by the nucleophilic attack of the C-3 oxygen on P gamma of the lambda isomer of the beta, gamma bidentate MgATP2- in a SN2(P) reaction that goes with inversion of configuration at P.