Effects of quinolinic acid and glucagon on gluconeogenesis in the perfused rat liver.
Previous findings that 2.5 mM quinolinic acid inhibits gluconeogenesis more strongly from alanine than from lactate have been confirmed. 15 mM quinolinic acid completely inhibited gluconeogenesis from lactate as well as from alanine whereas the formation of glucose from fructose and the production of urea from ammonia and lactose were not affected. The pattern of the gluconeogenic intermediates was the same in the presence of 15 mM quinolinic acid as with 2.5 mM of the inhibitor. It is concluded that high as well as low concentrations of quinolinic acid inhibit gluconeogenesis at the step between oxaloacetate and phosphoenolpyruvate. Furthermore, 5-methoxyindole-2-carboxylic acid, an inhibitor of mitochondrial pyruvate metabolism, also completely blocked gluconeogenesis from lactate whereas glycerol conversion to glucose was only weakly inhibited. All these results do not support the concept of an alternate pathway of gluconeogenesis from lactate proposed by others. 2.5 mM quinolinic acid also partially blocked the formation of urea from alanine. It is suggested that quinolinic acid may have a second site of action causing an inhibition of the glutamate-pyruvate transamination owing to lack of 2-oxoglutarate in the cytosol. In the presence of quinolinic acid, glucagon caused about the same increase in aspartate and malate tissue levels in the absence of added substrates as in the presence of added lactate or alanine. Therefore, no additional effect of glucagon on gluconeogenesis from lactate or alanine prior to the block by quinolinic acid could be demonstrated.
D000409:Alanine / Q000378:metabolism; D000818:Animals; D005934:Glucagon / Q000378:metabolism* / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011725:Pyridines / Q000378:metabolism*; D011805:Quinolinic Acids / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D007773:Lactates; D011725:Pyridines; D011805:Quinolinic Acids; D014508:Urea; D005934:Glucagon; D005947:Glucose; D000409:Alanine