L-arginine metabolism in dog kidney and isolated nephron segments.
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.
Levillain
Olivier
O
Université Claude Bernard Lyon 1, Laboratoire de Physiopathologie Métabolique et Rénale, Institut National de la Santé et de la Recherche Médicale (INSERM), 69372 Lyon Cedex 08, France. Olivier.Levillain@sante.univ-lyon1.fr
Rabier
Daniel
D
Duclos
Bernard
B
Gaudreau
Pierrette
P
Vinay
Patrick
P
D000596:Amino Acids / Q000097:blood; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001835:Body Weight; D004285:Dogs; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D009399:Nephrons / Q000378:metabolism*; D012077:Renal Artery / Q000502:physiology; D012082:Renal Veins / Q000502:physiology
D000596:Amino Acids; D001120:Arginine