title: Stimulation of human nitric oxide synthase by tetrahydrobiopterin and selective binding of the cofactor.
abstract: To check the stimulatory potency of the tetrahydro forms of the two major pteridines occurring in human tissues, neopterin and biopterin, NO synthase was purified 6000-fold from human cerebellum. Tetrahydrobiopterin stimulated the activity up to 4.5-fold in a concentration dependent manner with a maximum above 1 microM, whereas tetrahydroneopterin was completely inactive in concentrations up to 100 microM. Tetrahydrobiopterin, but not neopterin derivatives, were copurified with the NO synthase activity. Our results demonstrate that human cerebellum contains a tetrahydrobiopterin dependent NO synthase activity.
authors.affiliation: Institut für Pharmakologie, Freien Universität Berlin, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Klatt
authors.forename: B
authors.initials: B
authors.lastname: Heinzel
authors.forename: B
authors.initials: B
authors.lastname: Mayer
authors.forename: E
authors.initials: E
authors.lastname: Ambach
authors.forename: G
authors.initials: G
authors.lastname: Werner-Felmayer
authors.forename: H
authors.initials: H
authors.lastname: Wachter
authors.forename: E R
authors.initials: ER
authors.lastname: Werner
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002531:Cerebellum / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019001:Nitric Oxide Synthase
chemical_list: D001708:Biopterins; C023455:tetrahydroneopterin; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C003402:sapropterin