title: The regulation of vascular tetrahydrobiopterin bioavailability.
abstract: 6R l-erythro-5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for several enzymes including phenylalanine hydroxylase and the nitric oxide synthases (NOS). Oral supplementation of BH4 has been successfully employed to treat subsets of patients with hyperphenylalaninaemia. More recently, research efforts have focussed on understanding whether BH4 supplementation may also be efficacious in cardiovascular disorders that are underpinned by reduced nitric oxide bioavailability. Whilst numerous preclinical and clinical studies have demonstrated a positive association between enhanced BH4 and vascular function, the efficacy of orally administered BH4 in human cardiovascular disease remains unclear. Furthermore, interventions that limit BH4 bioavailability may provide benefit in diseases where nitric oxide over production contributes to pathology. This review describes the pathways involved in BH4 bio-regulation and discusses other endogenous mechanisms that could be harnessed therapeutically to manipulate vascular BH4 levels.
authors: Pharmacology and Therapeutics Group, Institute of Pharmaceutical Science, School of Biomedical Sciences, King's College London, Franklin Wilkins Building, 150 Stamford Street,London SE1 9NH, United Kingdom.
authors: Anna
authors: A
authors: Starr
authors: Dania
authors: D
authors: Hussein
authors: Manasi
authors: M
authors: Nandi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010651:Phenylalanine Hydroxylase / Q000378:metabolism; D010661:Phenylketonurias / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D001708:Biopterins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010651:Phenylalanine Hydroxylase; C003402:sapropterin