Stereospecificity of Enzymic Reactions involving Mevalonic Acid

Abstract

MOST of the biosynthetic studies with mevalonic acid have so far been carried out with the racemic substance labelled with carbon-14. There have been no reports indicating a utilization greater than 50 per cent of DL-mevalonate either in vivo or in vitro in any enzymic reaction. Thus, Tavormina, Gibbs and Huff¹, who made the discovery that mevalonate was an outstanding precursor of cholesterol, noted that about 43 per cent of the DL-[2-¹⁴C] mevalonate was converted in liver homogenates into cholesterol; an observation confirmed by Popják et al. ². Gould and Popják³ found that of the dose of carbon-14 contained in DL-[2-¹⁴C] mevalonate and injected into mice about 40 per cent appeared in body sterol, 10 per cent in expired carbon dioxide and 50 per cent in the urine. Both Tchen⁴ and Levy and Popjak^5,6 observed that in the mevalonic kinase reaction, in the phosphorylation of mevalonate with adenosine triphosphate to 5-phosphomevalonate, no more than 50 per cent of the DL-mevalonate was used by the enzyme. All these observations led to the conclusion that only one enantiomorph of mevalonate could act as substrate in biosynthetic reactions, and this was assumed to be the natural (+) isomer, [α]²⁴ _D, + 10° (Wolf et al.⁷).