title: Does vitamin C enhance nitric oxide bioavailability in a tetrahydrobiopterin-dependent manner? In vitro, in vivo and clinical studies.
abstract: Ascorbate (Asc) has been shown to increase nitric oxide (NO) bioavailability and thereby improve endothelial function in patients showing signs of endothelial dysfunction. Tetrahydrobiopterin (BH₄) is a co-factor of endothelial nitric oxide synthase (eNOS) which may easily become oxidized to the inactive form dihydrobiopterin (BH₂). Asc may increase NO bioavailability by a number of mechanisms involving BH₄ and eNOS. Asc increases BH₄ bioavailability by either reducing oxidized BH₄ or preventing BH₄ from becoming oxidized in the first place. Asc could also increase NO bioavailability in a BH₄-independent manner by increasing eNOS activity by changing its phosphorylation and S-nitrosylation status or by upregulating eNOS expression. In this review, we discuss the putative mechanisms by which Asc may increase NO bioavailability through its interactions with BH₄ and eNOS.
authors: Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors: Alan
authors: A
authors: Mortensen
authors: Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: jopl@sund.ku.dk.
authors: Jens
authors: J
authors: Lykkesfeldt
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001708:Biopterins / Q000031:analogs & derivatives* / Q000737:chemistry; D002318:Cardiovascular Diseases / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D009569:Nitric Oxide / Q000493:pharmacokinetics*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012306:Risk; D014664:Vasodilation
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D001708:Biopterins; D009569:Nitric Oxide; C017226:7,8-dihydrobiopterin; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin; D009584:Nitrogen; D001205:Ascorbic Acid; D010100:Oxygen
keywords: Ascorbate; Dihydrobiopterin; Nitric oxide bioavailability; Tetrahydrobiopterin