Role of Acetyl Coenzyme A Carboxylase in the Control of Fatty Acid Synthesis

Abstract

Publisher Summary This chapter discusses recent advances in studies on the regulatory mechanisms of a biotin enzyme, liver acetyl coenzyme A (CoA) carboxylase, which plays a critical role in the control of fatty acid synthesis. To study the control mechanisms of a metabolic sequence consisting of several steps catalyzed by different enzymes, it is important to know which step is rate-limiting in the overall process. Shortly after the discovery of the fatty acid-synthesizing pathway via malonyl-CoA, evidence was presented that indicated that the carboxylation step is rate-limiting in overall synthesis from acetyl-CoA in tissue extracts. Subsequent investigations revealed that carboxylase was not fully activated under the conditions employed in these experiments. This chapter presents evidence that indicates that the regulation of carboxylation step in vivo is achieved both by changes in the amount of acetyl-CoA carboxylase—that is, the number of enzyme molecules—and by changes in the activity of carboxylase—that is, catalytic efficiency per enzyme molecule. The former mechanisms appear to be more responsible for the long-term control, while the latter for the short-term one.