Responses of hepatic phosphoenolypyruvate carboxykinase activities from normal and diabetic rats to quinolinate inhibition and ferrous ion activation.
1. Phosphoenolpyruvate carboxykinase (GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32) from tryptophan-treated normal rats, when assayed immediately after preparation is not activated by Fe2+ but is inhibited 65% by 2.0 mM quinolinate whether or not Fe2+ is present. As time of storage increases, the enzyme's sensitivity to Fe2+ activation returns as does the ability of quinolinate to more effectively inhibit the Fe2+-activated enzyme. 2. Phosphoenolpyruvate carboxykinase from NaCl- and tryptophan-treated diabetic rats is activated about 2-fold by 20 microM Fe2+. Quinolinate (2.0 mM) inhibits the Fe2+-activated enzyme 65% compared to 20% inhibition of the non-Fe2+-activated enzyme. In these respects, the enzyme from NaCl- and tryptophan-treated diabetic rats acts in vitro just like the enzyme from NaCl-treated normal rats and unlike the enzyme from tryptophan-treated normal rats. Thus, the inability of tryptophan and quinolinate to inhibit gluconeogenesis and to alter the assayable activity of phosphoenolpyruvate carboxykinase from diabetic rats in vivo is inconsistent with quinolinate's ability to inhibit the enzyme in vitro. 3. Quinolinate's inhibition of phosphoenolpyruvate carboxykinase from NaCl, tryptoiphan-treated normal and diabetic rats is of a 'mixed' nature. 4. Hepatic cytosolic phosphoenolpyruvate carboxykinases from fasted normal guinea pigs, pigeons, and rabbits are activated 2-3-fold by Fe2+ and inhibition by quinolinate in the presence of Fe2+ ranges from 65-75% compared to no inhibition without Fe2+. Mitochondrial carboxykinases from these three species are only activated 20-30% by Fe2+, although quinolinate, which is ineffective as an inhibitor in the absence of Fe2+, inhibits the enzymes 40-50% in the presence of Fe2+.
D000818:Animals; D010856:Columbidae; D003600:Cytosol / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004789:Enzyme Activation; D005296:Ferrous Compounds / Q000378:metabolism*; D006168:Guinea Pigs; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D011805:Quinolinic Acids / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats
D005296:Ferrous Compounds; D011725:Pyridines; D011805:Quinolinic Acids; D007501:Iron; D010729:Phosphoenolpyruvate Carboxykinase (GTP)