Renal metabolism of glutamine in rats with acute renal failure

Abstract

Acute renal failure induced by glycerol results in increased metabolism of glutamine by renal cortical slices of rats 16 and 36 hr after onset, and there is also increased glutamine uptake by the kidney in vivo. Metabolism of glutamine and glutamate to glucose is inhibited. At 8 days after onset of renal failure, metabolism of glutamine returns to normal. Initially, activities of phosphate-dependent glutaminase (PDG) and glutamate dehydrogenase are depressed. The activity of glutaminase returns to normal by 8 days, but glutamate dehydrogenase activity is still inhibited. Increased ammoniagenesis and glutamine uptake are mainly a result of increased entry into the cell since activity of glutaminase is inhibited.

Metabolic Modulation of Cellular Function

“…However, during the metabolic acidosis phase of AKI, about onethird of plasma glutamine is taken up and metabolized by the kidney. The increased utilization of glutamine occurs primarily in the proximal convoluted tubules, where a significant increase in glutaminase activity has been observed (Anderson et al, 1982). The mechanism underlying this phenomenon may be related to z-crystal protein, which, under acidic conditions, enhances the binding with glutaminase mRNA sequence, inhibiting ribonuclease recruitment, and stabilizing glutaminase mRNA, resulting in increased glutaminase expression (Curthoys, 2001).…”

Energy metabolic reprogramming regulates programmed cell death of renal tubular epithelial cells and might serve as a new therapeutic target for acute kidney injury

“…However, during the metabolic acidosis phase of AKI, about one-third of plasma glutamine is taken up and metabolized by the kidney. The increased utilization of glutamine occurs primarily in the proximal convoluted tubules, where a significant increase in glutaminase activity has been observed ( Anderson et al, 1982 ). The mechanism underlying this phenomenon may be related to z-crystal protein, which, under acidic conditions, enhances the binding with glutaminase mRNA sequence, inhibiting ribonuclease recruitment, and stabilizing glutaminase mRNA, resulting in increased glutaminase expression ( Curthoys, 2001 ).…”

Glutamina sérica como factor predictivo de insuficiencia renal en pacientes oncológicos tratados con quimioterapia basada en cisplatino

“…Tales hallazgos pueden explicarse, bien por un incremento en la tendencia anabólica a consecuencia de la insuficiencia renal, que tiende a no catabolizar la glutamina, o por un efecto tóxico directo de la gentamicina sobre las enzimas de decarboxilación, es decir la glutaminasa entre otras 32 . Pero la alteración de la glutaminasa no es permanente mientras dure la insuficiencia renal, sino que acontece en etapas muy iniciales, y la actividad enzimática retorna a la normalidad en pocos días, con los cual sus efectos sobre la glutamina sólo se apreciarán precozmente 33 . Esta sería la base para fundamentar que en nuestro estudio la elevación de la glutamina fue más evidente en los momentos precedentes al desarrollo de la insuficiencia renal manifiesta, cuando el daño tubular ya existía previamente, y sin embargo cuando el fallo renal ya se ha establecido, la glutamina disminuía su concentración.…”