Regulation of phosphoenolpyruvate carboxykinase by glutamine and ATP as possible control mechanisms of renal gluconeogenesis.
In different metabolic states renal phosphoenolpyruvate carboxykinase (PEP-CK) activities are closely correlated with in vitro glucogenic rates, suggesting a limitation of the glucogenic capacity of kidney by this enzyme. Stimulation of renal gluconeogenesis from pyruvate, lactate, and succinate by lysine and glutamine was therefore associated with a regulatory attack of these amino acids at the level of PEP-carboxykinase. This postulate was confirmed by the failure of lysine to stimulate glucose synthesis from fructose. Experimental support for an interference of glutamine and PEP-carboxykinase was obtained by a study on the inactivation of this enzyme in kidney cortex homogenates: A rapid inactivation of enzyme activity within 40-50 min could be slowed down by glutamine. In addition the inactivation was counteracted by ATP. At suboptimal concentrations of the trinucleotide its effect was potentiated by c-AMP and c-GMP. Studies on the effect of ATP on PEP-carboxykinase in kidney cortex homogenates from rats in different metabolic states revealed: In homogenates from carbohydrate fed animals extreme low activities of PEP-CK were not altered by ATP, whereas elevated enzyme activities after a protein rich diet could be further raised by a factor of 2 or 3 by ATP. GTP and ITP could substitute for ATP. An extension of these studies on hepatic enzymes showed a similar inactivation of tyrosine aminotransferase (TAT) and a protective effect of ATP. The data obtained from these experiments favour an interconversion of PEP-carboxykinase and tyrosine aminotransferase into different forms as possible mechanism for their regulation.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D004040:Dietary Carbohydrates; D005246:Feedback; D005632:Fructose / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects*; D005973:Glutamine / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000494:pharmacology; D008239:Lysine / Q000494:pharmacology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism*; D051381:Rats; D012265:Ribonucleotides / Q000494:pharmacology; D013386:Succinates / Q000378:metabolism
D004040:Dietary Carbohydrates; D007773:Lactates; D012265:Ribonucleotides; D013386:Succinates; D005973:Glutamine; D005632:Fructose; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D008239:Lysine