Inhibition of glutamine synthetase activity by manganous ions in a cytosol extract of rat liver

Abstract

Glutamine synthetase activity in a cytosol extract of liver was inhibited non-competitively by Mn2+ ions. The apparent Ki for Mn2" in the presence of phosphate was 8 micro M. Inhibition of glutamine synthetase by intracellular Mn2+ may contribute to the very low rates of glutamine synthesis observed in perfused liver and isolated hepatocytes.

Differential interaction of hGDH1 and hGDH2 with manganese: Implications for metabolism and toxicity

“…This disturbance of glutamate transport may contribute to the excitotoxictype neuropathology observed in manganism. In addition, Mn could affect astrocytic metabolism by inhibiting GS (Joseph et al, 1979;Tholey et al, 1987) and pyruvate carboxylase (PC) (Wimhurst and Manchester, 1970), which are vital for astrocytic glucose oxidation and brain energy metabolism. Concerning the specific effects of Mn on mitochondrial function, Mn was shown to exert inhibitory effects on oxidative phosphorylation (Gavin et al, 1992).…”