Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1152/ajpcell.00405.2009

Type

Journal article

Journal

American Journal of Physiology-Cell Physiology

Publisher

American Physiological Society

Publication Date

07/2010

Volume

299

Pages

C148 - C154