Differential Effects of Palmityl Coenzyme A on Liver Microsomal Inorganic Pyrophosphate-Glucose Phosphotransferase and Glucose 6-Phosphate Phosphohydrolase

Abstract

Abstract The effects of palmityl coenzyme A on both hydrolytic and inorganic pyrophosphate-glucose phosphotransferase activities of glucose 6-phosphate phosphohydrolase (EC 3.1.3.9) of rat liver microsomes have been investigated. It was found that the acyl coenzyme A compound may either stimulate or inhibit, in a pH- and concentration-dependent, activity-discriminating manner. Marked activation of the phosphotransferase activity (to a maximum of 350% of control levels in one instance) was observed under a wide variety of conditions, while the glucose 6-phosphate phosphohydrolase activity was at best but modestly elevated (to a maximum of 120% of control levels) and was significantly inhibited by palmityl coenzyme A under most conditions tested. A concomitant extensive activation of phosphotransferase and inhibition of phosphohydrolase activity was observed with certain levels of the acyl coenzyme A compound. Effective concentrations of palmityl coenzyme A coincided with established levels of hepatic long chain fatty acyl coenzyme A derivatives. Coenzyme A, palmitate, and acetyl coenzyme A were without effect on enzymic activities. Maximal phosphotransferase activity was observed at pH 4.3 with untreated microsomal preparations. This maximum was shifted to pH 6 when assays were carried out in the presence of 4.1 x 10-5 m palmityl coenzyme A, and a significant amount of activity was observed at pH 7.0 under these conditions. It is suggested that changes, in vivo, of functional levels of the hydrolytic and synthetic activities of this enzyme in animals in various altered hormonal states, for example, diabetes, possibly may be mediated in part through these activity-discriminating effects of long chain acyl coenzyme A compounds.