Regulation of 2-oxoglutarate metabolism in rat liver by NADP-isocitrate dehydrogenase and aspartate aminotransferase.
Kinetic and regulatory properties of NADP-isocitrate dehydrogenase (NADP-IDH) and aspartate aminotransferase (AsAT) responsible for 2-oxoglutarate metabolism in the cytoplasm and mitochondria of rat liver were studied. Based on the subcellular location of these enzymes and their kinetic parameters (Km, Ksi) obtained with highly purified enzyme preparations, it is suggested that synthesis of 2-oxoglutarate should be mainly determined by cytoplasmic NADP-IDH (86% of the total activity in the cell), whereas its utilization should depend on cytoplasmic AsAT (78% of the total activity). AsAT from the rat liver was specified by substrate inhibition and also by changes in the enzyme affinity for the substrates under the influence of some intermediates of the tricarboxylic acid cycle: isocitrate, succinate, fumarate, and citrate. Key intermediates of nitrogen metabolism (glutamate, glutamine, and aspartate) are involved in the regulation of NADP-IDH and AsAT. These enzymes are regulated oppositely, and the catalytic activity of one enzyme can be stimulated concurrently with a decrease in the activity of the other. Obviously, carbon and nitrogen metabolism in the rat liver can be controlled through redistribution of 2-oxoglutarate between different metabolic processes via regulatory mechanisms influencing differently located forms of NADP-IDH and AsAT.
Rakhmanova
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TI
Department of Analytical and Medical Biochemistry and Microbiology, Faculty of Biology and Soil Sciences, Voronezh State University, 394693 Voronezh, Russia. rtyana@mail.ru
Popova
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TN
D000818:Animals; D001219:Aspartate Aminotransferases / Q000737:chemistry* / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology; D007521:Isocitrate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D051381:Rats
D007527:Isoenzymes; D007656:Ketoglutaric Acids; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); D001219:Aspartate Aminotransferases