Effect of chronic renal failure on arginase and argininosuccinate synthetase expression.

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Moradi H, Kwok V, Vaziri ND

Effect of chronic renal failure on arginase and argininosuccinate synthetase expression.

Am J Nephrol. 2006;26(3):310-8. Epub 2006 Jun 29.

PubMed ID

16809898 [ View in PubMed

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Abstract

BACKGROUND: L-arginine (L-arg) participates in numerous biological functions including urea and nitric oxide synthesis. Sources of L-arg include dietary proteins and endogenous synthesis by argininosuccinate synthetase and argininosuccinate lyase. L-arg is converted to urea by arginase I in the liver and arginase II in the kidney. Normally, the liver fully consumes L-arg for urea generation and does not contribute to its circulating pool. Instead, much of the circulating L-arg is produced by the kidney. If true, plasma L-arg should be severely reduced in chronic renal failure (CRF); however, plasma L-arg is frequently unchanged in CRF. We hypothesized that preservation of plasma L-arg in CRF may be, partly, due to downregulation/inhibition of arginase. METHODS: Argininosuccinate synthetase, arginase I and II protein abundance and activity were measured in the liver and kidneys of rats 6 weeks after 5/6 nephrectomy or sham operation. In addition, arginase activity was measured in the presence of different urea concentrations to simulate azotemia in vitro. RESULTS: Arginases I and II protein abundance as well as arginase activity in the liver, measured in the physiological buffer, were similar among the CRF and control groups. However, in vitro experiments simulating a uremic milieu revealed a marked concentration-dependent inhibition of arginase activity by urea in the tissue lysates. CRF had no significant effect on argininosuccinate synthetase abundance in the kidney, liver, spleen or intestine. CONCLUSIONS: Although CRF does not change the abundance or intrinsic properties of arginase, the inherent rise in urea concentration inhibits its enzymatic activity. The latter, in turn, attenuates L-arg catabolism and urea production and, thereby, mitigates the fall in plasma L-arg.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Arginine	Argininosuccinate lyase	Protein	Humans	Unknown	Not Available	Details
Arginine	Argininosuccinate synthase	Protein	Humans	Unknown	Not Available	Details