Inhibition by streptozotocin of the activity of succinyl‐Co A synthetase in vitro and in vivo

The activity of succinyl-CoA synthetase from mouse liver and kidney was inhibited by streptozotocin in vitro. Streptozotocin behaved essentially as a non-competitive inhibitor, and the following kinetic values were obtained (in the presence of 10 nM streptozotocin): apparent Km 1.7 mM, apparent Ki 10 nM, and kcat 440 nkat X kg-1. Compared with non-diabetic control mice, the succinyl-CoA synthetase activity was significantly decreased in the islets and kidneys of mice with early (1 h) and manifest (greater than or equal to 2 days) streptozotocin diabetes, whereas the activity in the liver was not significantly altered. Inhibited succinyl-CoA synthetase activity is believed to play a prominent role in the cellular effects of streptozotocin.