Effect of phosphoenolpyruvate carboxykinase inhibition on renal metabolism of glutamine: in vivo studies in the dog and rat.

Abstract

The effect of in vivo administration of mercaptopicolinate (MCP), a potent inhibitor of phosphoenolpyruvate carboxykinase (PEPCK) and of gluconeogenesis, on renal ammonia production was studied in dog and rat. In the dog, MCP depressed only slightly renal ammonia production, but increased strikingly renal glutamine extraction. Aspartate and alanine synthesis by the kidney were also considerably enhanced. The renal tissue metabolite profile showed an accumulation of oxaloacetate and malate but glutamate concentration was decreased. In the rat, MCP depressed renal glutamine extraction but did not abolish ammonia production in a proportionate fashion. Thus other amino acids support ammoniagenesis during PEPCK inhibition. The renal metabolite profile indicated inhibition of gluconeogenesis at the PEPCK step. It is concluded that in both species renal ammonia production can proceed through "non-PEPCK-dependent" pathways in vivo, at least during PEPCK inhibition.