Stimulation of human nitric oxide synthase by tetrahydrobiopterin and selective binding of the cofactor.
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.
Klatt
P
P
Institut für Pharmakologie, Freien Universität Berlin, Germany.
Heinzel
B
B
Mayer
B
B
Ambach
E
E
Werner-Felmayer
G
G
Wachter
H
H
Werner
E R
ER
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
D001708:Biopterins; C023455:tetrahydroneopterin; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C003402:sapropterin