Studies on the biosynthesis of cholesterol. 10. Mevalonic kinase and phosphomevalonic kinase from liver

Abstract

The enzyme which phosphorylates mevalonic acid in the 5-position, mevalonic kinase, has been partially purified from extracts of pig liver and its properties have been studied. Liver mevalonic kinase is probably a sulfhydryl enzyme requiring cysteine for activation under aerobic conditions. Adenosine triphosphate (or inosine triphosphate) is its coenzyme, with Mg++ as activator. Ca++, or less effectively, Mn++, also activate the enzyme; its pH optimum is 7.3. Mevalonic kinase is distinct from hexokinase, and it cannot phosphorylate a number of substances related to mevalonate. It is active on only one enantiomorph of DL-mevalonate. Potassium farnesoate, and particularly the salt of its saturated analogue, 3:7:ll-trimethyldodecanoate, inhibited mevalonic kinase. A large-scale preparation and purification of 5-phospho[2-Cl4] mevalonate formed from DL-[2-Cl4]mevalonate with mevalonic kinase is described. The properties of a second enzyme, which phosphorylates 5-phosphomevalonate to the 5-1 diphosphomevalonate, are briefly described. This enzyme has been named 5-phosphomevalonic kinase. The properties of liver mevalonic kinase are discussed in relation to a similar enzyme partially purified from yeast extracts by Tchen (1958).