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

Abstract

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 K m 1.7 mM, apparent K i 10 nM, and k cat 440 nkat·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 (≧ 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.

Accumulation of Succinyl Coenzyme A Perturbs the Methicillin-Resistant Staphylococcus aureus (MRSA) Succinylome and Is Associated with Increased Susceptibility to Beta-Lactam Antibiotics

“…8 ). The U.S. Food and Drug Administration-approved anticancer drug streptozotocin specifically targets succinyl-CoA synthetase in human cells to limit proliferation ( 63 ) and is used primarily to treat tumors that cannot be surgically removed. The findings described here may open the door to the possibility of sensitizing MRSA to β-lactam antibiotics using compounds that specifically target succinyl-CoA synthetase or protein succinylation generally within the cell.…”

Effects of sodium nitroprusside on blood glucose concentration, B‐cell morphology and islet glutamate dehydrogenase activity in mice

“…Preceding studies have suggested that the diabetogenicity of alloxan and streptozotocin is associated with morphological and functional changes in the B-cell mitochondria, with inhibited activity of citric acid cycle enzymes, disturbed Ca2+ transport and deficient NAD-linked respiration as salient features (3,4,7). Streptozotocin is a succinyl-CoA synthetase inhibitor (6), which may also inhibit the activity of citrate synthetase, secondarily to the accumulation of succinyl-CoA (7). Alloxan inhibits the activity of aconitase and some other enzymesof the citric acid cycle, including a-ketoglutarate dehydrogenase and succinyl-CoA synthetase ( 5 ) .…”

“…Glucose enhances the content of GTP in mouse islets (29), and the renal concentration of this nucleotide is decreased in streptozotocin diabetic mice (7). In this connection it should be recalled that succinyl-CoA synthetase, which is inhibited by streptozotocin (6), catalyzes the cleavage of the thioester bond of succinyl-CoA, associated with the phosphorylation of GDP. Moreover.…”