COMPARISON OF INFLUENCE OF 2-OXOGLUTARATE AND GLUTAMATE ON ARGINASE ACTIVITIES IN LIVER AND KIDNEY-CORTEX OF RABBIT, ORYCTOLAGUS-CUNICULUS

The effect of branched-chain amino acids, 2-oxoglutarate, glutamate an d lysine on arginase activity was studied in liver and kidney-cortex o f rabbit. In contrast to liver, where arginase was localized in both c ytosol and mitochondria, the enzyme activity in rabbit kidney-cortex w as exclusively exhibited in the mitochondrial fraction and was not act ivated by Mn2+ ions. The branched-chain amino acids (leucine, isoleuci ne and valine) significantly inhibited urea production in both kidney- cortex and liver mitochondria and in the liver cytosolic fraction, whe reas lysine was less effective. In contrary, the urea production in in tact and permeabilized kidney-cortex mitochondria was decreased by abo ut 30-50% by glutamate and 2-oxoglutarate added at 2 mM concentrations , whereas arginase activities in both cytosolic and mitochondrial frac tions of rabbit liver were not affected by these compounds in the pres ence and absence of Mn2+ ions. 2-Oxoglutarate appeared to be a poor no ncompetitive inhibitor of kidney-cortex arginase (K-i = 6.2 +/- 0.9 mM ), whereas glutamate was the competitive one (K-i = 1.5 +/- 0.1 mM). W hen methionine sulfoximine, an inhibitor of glutamine synthetase, was added to renal tubule suspension to accumulate glutamate inside mitoch ondria, the urea production was lower than that on the inhibition of g lutamate generation by aminooxyacetate, an inhibitor of aminotransfera ses, despite an increase oi ornithine content in the particulate fract ion, indicating that kidney-cortex arginase might be affected by gluta mate under physiological conditions. Copyright (C) 1996 Elsevier Scien ce Inc.