Liver Microsomal Glucose-6-phosphatase: Protection by Inhibitors and Substrates Against Thermal Inactivation 1

Abstract

Summary

The ability of a variety of inhibitors and substrates to stabilize liver microsomal glucose-6-phosphatase (D-glucose-6-P phosphohydrolase, EC 3.1.3.9) against thermal inactivation has been investigated. Studies were carried out by incubating microsomal suspensions in sodium cacodylate buffer at pH 6.5 for 20 min at 40°, either in the absence or presence of various concentrations of certain inhibitors or substrates, cooling; and then assaying for enzymic activity. Significant protection was afforded by the inhibitors citrate, bicarbonate, P₁, and ammonium molybdate, and by the phosphoryl substrates glucose-6-P, PP₁, ADP, and ATP. d-Glucose had little effect, and inhibition by 1,10-phenanthroline was irreversible. These observations support the reaction mechanism previously suggested for this multifunctional catalyst, and indicate the advisability of including phosphoryl substrates or certain competitive inhibitors as stabilizers of the enzyme preparations during future attempts at purification.