Deficient acetyl CoA carboxylase activity in multiple carboxylase deficiency

Abstract

Multiple carboxylase deficiency has previously been characterized by deficient activity of three biotin-dependent enzymes: propionyl CoA carboxylase, pyruvate carboxylase and β-methylcrotonyl CoA carboxylase. We have demonstrated that the activity of a fourth carboxylase, acetyl CoA carboxylase (ACC), is also deficient in fibroblasts from two patients with this disorder. Furthermore, ACC activity increased six- to eight-fold when cells from these patients were incubated in culture medium containing supplemental biotin. If the primary defect in multiple carboxylase deficiency is due to deficient activity of holocarboxylase synthetase, our results would indicate that there may be a common holocarboxylase synthetase, or at least a common subunit, for all the carboxylases. Finally, since ACC catalyzes the initial step in fatty acid biosynthesis, our results further suggest the importance of dietary supplementation with fatty acids in addition to treating these patients with pharmacologie doses of biotin.