Maleate-induced stimulation of glutamine metabolism in the intact dog kidney.
Studies were performed in anesthetized normal dogs to evaluate the effects of maleate on renal metabolism. Intravenous administration of maleate (50 mg/kg) markedly increased urinary excretion of glutamine, glutamate, alpha-ketoglutarate, alanine, lactate, pyruvate, and citrate. Despite a fourfold rise in renal cortical concentration of alpha-ketoglutarate, glutamine utilization expressed per 100 ml glomerular filtration rate almost doubled following maleate administration, whereas total ammonia production increased threefold, most of this ammonia being diverted into the renal vein. The renal production of alpha-ketoglutarate rose in a spectacular fashion and was almost equal to the renal utilization of glutamine, indicating a metabolic block at the alpha-ketoglutarate dehydrogenase step. Maleate reduced renal alanine production but did not change lactate utilization. These findings suggest that 1) in the intact dog the mitochondrial entry of glutamine is not regulated only by alpha-ketoglutarate; 2) the deamination of glutamate into alpha-ketoglutarate is accelerated by maleate, probably through an impaired mitochondrial NADH production; 3) the resulting decrement in intramitochondrial glutamate concentration deinhibits the phosphate-dependent glutaminase.
D000818:Animals; D001158:Arteries; D001774:Blood Chemical Analysis; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005973:Glutamine / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014556:Urine / Q000032:analysis
D008298:Maleates; D005973:Glutamine