Cytoplasmic 3-Hydroxy-3-methylglutaryl Coenzyme A Synthase from Liver

The cytoplasmic fraction of avian liver contains multiple forms of 3-hydroxyd-methylglutaryl coenzyme A synthase which are distinct from their mitochondrial counterpart. Of the four cytoplasmic species, synthases I and II predominate, constituting 22 and 62%, respectively, of the total cytoplasmic synthase activity; synthases III and IV are minor forms comprising the remaining 16%. Each of the cytoplasmic synthases was purified to homogeneity from chicken liver and found to be a dimeric protein of approximately 100,000 daltons composed of identical molecular weight subunits. Despite this similarity the enzymes differ with respect to isoelectric point, elution behavior upon ion exchange chromatography, and migration upon disc gel electrophoresis. Synthase I, although not identical to the mitochondrial synthase, possesses several properties in common with it. These include immunochemical cross-reactivity, inhibition by MgC12, and dissociation to monomeric form by KCl. Cytoplasmic synthases II, III, and IV are immunochemically related but, unlike synthase I, do not cross-react with antiserum against the mitochondrial synthase. Moreover, synthases II, III, and IV are activated by MgClz and are not dissociated by KCl. Cytoplasmic synthase II is converted to the related species, synthases III and IV, by a nondialyzable cytosolic component. The livers of other avian species, e.g. pigeon and turkey, also possess multiple cytoplasmic 3-hydroxyd-methylglutaryl-CoA synthases, as indicated by their cross-reactivity with antibodies against the chicken liver cytoplasmic synthases. All tissues of the chicken examined were found to contain cytoplasmic 3-hydroxy-3-methylglutaryl-CoA synthase; however, only liver and kidney possessed mitochondrial synthase. The tissue distributions of the cytoplasmic and mitochondrial synthases are com-