Regulation of coenzyme A synthesis in heart muscle: effects of diabetes and fasting

Abstract

Regulation of coenzyme A (CoA) synthesis was studied in the isolated perfused rat heart. Incorporation of [14C]pantothenic acid ([14C]PA) into CoA was determined to estimate rates of CoA synthesis. Although CoA levels were elevated in hearts removed from fasted and diabetic animals, in vitro rates of CoA synthesis were not elevated. The presence of 1.2 mM palmitate, 5 mM pyruvate, or 10 mM beta-hydroxybutyrate in the perfusate-reduced PA incorporation into CoA in control hearts by 40, 60, and 80%, respectively. Insulin (25 mU/ml) reduced incorporation by 90%. The alterations in CoA synthesis in hearts perfused with buffer containing palmitate, pyruvate, beta-hydroxybutyrate, and insulin were associated with no change in myocardial PA uptake. Data indicate that these substrates and insulin inhibit the first step in the pathway of CoA synthesis, pantothenate kinase. Because insulin is a strong inhibitor of CoA synthesis in vitro, decreased circulating levels of insulin in fasted and diabetic animals may account for the increased levels of CoA in vivo.