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Nitrite-NO bailout for a NOS complex too big to fail

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Cellular production of nitric oxide (NO) by nitric oxide synthase (NOS) in the face of limiting pools of arginine requires the intracellular citrulline-to-NO pathway, catalyzed by the enzyme argininosuccinate lyase (ASL). People with the urea cycle disorder argininosuccinic aciduria, caused by a deficiency of ASL, have systemic NO deficiency, which can be rescued by the use of an alternative, NOS-independent, nitrite-to-NO pathway.

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Figure 1: Intracellular arginine, produced by citrulline metabolism or imported through CAT1, is oxidized to citrulline and NO by eNOS.

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Authors and Affiliations

  1. Mark T. Gladwin and Jesús Tejero are in the Vascular Medicine Institute and the Division of Pulmonary, Allergy and Critical Care Medicine, Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.,

    Mark T Gladwin & Jesús Tejero

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  1. Mark T Gladwin
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  2. Jesús Tejero
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Correspondence to Mark T Gladwin.

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Competing interests

M.T.G. is listed as a co-inventor on an US National Institutes of Health government patent for the use of nitrite salts in cardiovascular conditions. He has a collaborative agreement between the US government and INO Pharmaceuticals and a collaborative agreement with Bayer.

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Gladwin, M., Tejero, J. Nitrite-NO bailout for a NOS complex too big to fail. Nat Med 17, 1556–1557 (2011). https://doi.org/10.1038/nm.2591

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