Endothelial nitric oxide synthase reduces nitrite anions to NO under anoxia.
In this work, we demonstrate that endothelial nitric oxide synthase is capable of anoxic reduction of nitrite anions to nitric oxide at physiological pH by absorption and EPR spectroscopy and electrochemical measurements. The nitrite reduction is achieved at the oxygenase domain of the protein and proceeds even in the absence of the tetrahydrobiopterin cofactor. The nitrite pathway increases by sixfold the NO production with respect to the regular arginine pathway under hypoxia, which is largely blocked. Therefore, basal levels of NO release could be sustained by anoxic nitrite reduction. The reaction suggests a new pathway for fast NO delivery under hypoxia, precisely when the vasodilating properties of nitric oxide are most needed.
Gautier
Clément
C
Laboratory for Optics and Biosciences, INSERM U696, CNRS UMR 7645, Ecole Polytechnique, Palaiseau, France.
van Faassen
Ernst
E
Mikula
Ivan
I
Martasek
Pavel
P
Slama-Schwok
Anny
A
D000693:Anaerobiosis / Q000187:drug effects; D000838:Anions / Q000737:chemistry / Q000378:metabolism; D015687:Cell Hypoxia; D009249:NADP / Q000378:metabolism / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000737:chemistry / Q000378:metabolism*; D009573:Nitrites / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D010105:Oxygenases / Q000378:metabolism; D013057:Spectrum Analysis
D000838:Anions; D009573:Nitrites; D009569:Nitric Oxide; D009249:NADP; D010105:Oxygenases; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen