Publication: Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme
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Issued Date
2010-07-01
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ISSN
15221563
03636143
03636143
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2-s2.0-77953786118
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Mahidol University
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SCOPUS
Bibliographic Citation
American Journal of Physiology - Cell Physiology. Vol.299, No.1 (2010)
Suggested Citation
F. Omodeo-Salè, L. Cortelezzi, Z. Vommaro, D. Scaccabarozzi, A. M. Dondorp Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme. American Journal of Physiology - Cell Physiology. Vol.299, No.1 (2010). doi:10.1152/ajpcell.00405.2009 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/28674
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Title
Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme
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Abstract
Severe Plasmodium falciparum malaria is associated with hypoargininemia, which contributes to impaired systemic and pulmonary nitric oxide (NO) production and endothelial dysfunction. Since intravascular hemolysis is an intrinsic feature of severe malaria, we investigated whether and by which mechanisms free heme [Fe(III)-protoporphyrin IX (FP)] might contribute to the dysregulation of L-arginine (L-Arg) metabolism and bioavailability. Carrier systems "y+" [or cationic amino acid transporter (CAT)] and "y+L" transport L-Arg into red blood cells (RBC), where it is hydrolyzed to ornithine and urea by arginase (isoform I) or converted to NO•and citrulline by endothelial nitric oxide synthase (eNOS). Our results show a significant and dose-dependent impairment of L-Arg transport into RBC pretreated with FP, with a strong inhibition of the system carrier y+L. Despite the impaired L-Arg influx, higher amounts of L-Arg-derived urea are produced by RBC preexposed to FP caused by activation of RBC arginase I. This activation appeared not to be mediated by oxidative modifications of the enzyme. We conclude that L-Arg transport across RBC membrane is impaired and arginase-mediated L-Arg consumption enhanced by free heme. This could contribute to reduced NO production in severe malaria. Copyright © 2010 the American Physiological Society.