Evidence of activation of the renal glutamate dehydrogenase pathway in intact acidotic dogs.
To determine if activity of the renal glutamate dehydrogenase (GD) pathway changes during chronic acidosis in intact dogs, we assessed the deamination of glutamate formed within renal cells during glutamine and alanine infusions. Infusing glutamine into chronically acidotic, normal and acutely alkalotic dogs enhanced renal ammonia production; more was formed as glutamine loading increased. In 4 acidotic dogs, the ratio of ammonia produced to glutamine extracted by the kidneys during exogenous glutamine loading was 1.93 compared with 0.99 for 5 alkalotic dogs and 1.23 for 2 control dogs. Little glutamate and alanine were released into the renal vein in acidotic dogs, whereas over 50% of the exogenous glutamine extracted in acutely alkalotic dogs could be accounted for as glutamate and alanine released into the renal vein. Renal glutamate concentrations were not elevated in acidosis compared with alkalosis despite greater deamidation. When glutamine infusions increased renal ammoniagenesis in acutely alkalotic and control dogs to levels seen in chronically acidotic dogs receiving no exogenous glutamine, approximately 4 to 6 times more glutamate was released from the kidneys. Infusing alanine into 7 chronically acidotic dogs enhanced ammoniagenesis significantly (p less than 0.01), but lesser augmentation was seen in 3 control dogs and no augmentation was seen in 6 acutely alkalotic dogs. The increases were secondary to enhanced glutamate deamination, not secondary to any changes in glutamine extraction and/or transaminase activity. We conclude that the glutamate dehydrogenase pathway is more active in intact acidotic dogs than it is in control and alkalotic dogs.
D000138:Acidosis / Q000201:enzymology*; D000409:Alanine / Q000494:pharmacology; D000471:Alkalosis / Q000201:enzymology; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D003641:Deamination; D004285:Dogs; D004789:Enzyme Activation; D005260:Female; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D005971:Glutamates; D005973:Glutamine / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D008297:Male
D005971:Glutamates; D005973:Glutamine; D000641:Ammonia; D005969:Glutamate Dehydrogenase; D000409:Alanine