Hexose metabolism in pancreatic islets. Regulation of NAD-isocitrate dehydrogenase activity.
D-Glucose causes a preferential stimulation of mitochondrial oxidative events relative to glycolysis in pancreatic islets. The possible participation of a Ca(2+)-induced activation of NAD-isocitrate dehydrogenase in this process was investigated. The activity of the enzyme in rat islet homogenates was measured through the generation of either NADH or 2-ketoglutarate. In the absence of Ca2+ and ADP, half-maximal velocities were recorded at isocitrate and NAD+ concentrations close to 1.2 and 0.5 mM, respectively. At isocitrate concentrations in the 0.15-1.5 mM range, ADP (1.0 mM) markedly increased the reaction velocity recorded in the absence of Ca2+ and conferred to the enzyme the property of being activated by Ca2+, with a Ka for Ca2+ somewhat below 1.0 microM. From these data and by comparison with the activity of 2-ketoglutarate dehydrogenase, it is proposed that activation of NAD-isocitrate dehydrogenase by such factors as ADP and Ca2+ may be required in order to match, in nutrient-stimulated islets, the rates of 2-ketoglutarate generation and oxidative decarboxylation.
Rasschaert
J
J
Laboratory of Experimental Medicine, Erasmus Medical School, Brussels Free University, Belgium.
Malaisse
W J
WJ
D000818:Animals; D006601:Hexoses / Q000378:metabolism*; D007515:Islets of Langerhans / Q000201:enzymology*; D007521:Isocitrate Dehydrogenase / Q000032:analysis*; D007656:Ketoglutaric Acids / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D051381:Rats
D006601:Hexoses; D007656:Ketoglutaric Acids; D009243:NAD; D007521:Isocitrate Dehydrogenase