Abstract
The effect of quinolinic acid and its ferrous and manganous derivatives on phosphoenolpyruvate (PEP) carboxylase (GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32) from rat liver cytoplasm is dependent upon the concentration of oxaloacetate in the assay system. At limiting levels of oxaloacetate all three compounds are inhibitory. At saturating levels of oxaloacetate the concentration of quinolinic acid and ferrous quinolinate required to inhibit PEP formation is increased and manganous quinolinate actually stimulates the reaction. Reciprocal plots show that ferrous quinolinate is a competitive inhibitor and manganous quinolinate produces a mixed type of inhibition. Removal of one of the carboxyl groups of quinolinic acid so that it no longer has the same dicarboxylic structure as oxaloacetate markedly decreases its ability to inhibit PEP carboxylase. The calculated K i for ferrous quinolinate is 1·10 −4 M. The intraperitoneal injection of 10 mg of l-tryptophan/100 g of body weight produces a quinolinic acid concentration of 3.7·10 −4 M and a 5-fold rise in the level of malate in the liver indicating the cytoplasmic PEP carboxylase is blocked. Concentrations of quinolinic acid in the liver below 1·10 −4 M may also influence this reaction through the chelation of ferrous ions as suggested by Lardy.
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