AJP - Renal Physiology, Vol 248, Issue 4 585-F593, Copyright © 1985 by American Physiological Society
Maleate-induced stimulation of glutamine metabolism in the intact dog kidney
A. Gougoux, P. Vinay and M. Duplain
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.
