L-Arginine metabolism in dog kidney and isolated nephron segments

Abstract

The renal basic amino acid metabolism often differs in rodents, strict carnivores, and omnivore species. Given the pivotal role of l-arginine and l-ornithine in several metabolic pathways and the fact that the dog is closely related to humans, being also an omnivore, we tested whether l-arginine metabolism and l-ornithine catabolism take place in the dog kidney. We examined the metabolism of l-arginine in dog cortical tubules to integrate local l-arginine metabolism into a general physiological and metabolic framework. To achieve these goals, we first ascertained the protein expression of relevant enzymes by Western blot. l-Arginine catabolism was studied in suspensions of canine cortical proximal tubules, medullary thick ascending limbs, and papillary collecting ducts either incubated without exogenous l-arginine being added (small endogenous quantities) or incubated with l-arginine being added in supraphysiological amounts (2 mmol/L with or without the presence of alternative metabolic substrates, 2 mmol/L l-glutamine, or lactate). The results revealed that dog kidneys consumed l-citrulline and released l-arginine and l-ornithine. Argininosuccinate synthetase and lyase, arginase II, and ornithine aminotransferase were detected in the renal cortex. Arginase II activity was found in a suspension of proximal tubules by measuring the amounts of urea and l-ornithine produced. A fraction of this l-ornithine was further partially metabolized through the intramitochondrial ornithine aminotransferase pathway, leading to changes in l-glutamate, glucose, l-alanine, and ammonia metabolism without l-proline accumulation. Medullary thick ascending limbs expressed a very low arginase activity, whereas papillary collecting ducts did not. In conclusion, the dog kidney produces l-arginine. Part of this l-arginine is further catabolized by arginase II, suggesting that its physiological role was to produce l-ornithine for the body.