A Tetrahydrobiopterin Radical Forms and then Becomes Reduced during Nω-Hydroxyarginine Oxidation by Nitric-oxide Synthase

Tetrahydrobiopterin and endothelial nitric oxide synthase activity.

Tetrahydrobiopterin and endothelial nitric oxide synthase uncoupling.

Tetrahydrobiopterin and Endothelial Nitric Oxide Synthase Uncoupling To the Editor: Gao et al1 reported that oral administration of folate, the tetrahydrobiopterin (H4B) precursor, attenuated endothelial NO synthase (eNOS) uncoupling in abdominal aortic aneurysm. The beneficial effects of H4B supplementation in endothelial dysfunction are beyond dispute, but in vivo demonstration of eNOS (un)co...

Nω-nitro-nω'-substituted Guanidines: a Simple Class of Nitric Oxide Synthase Inhibitors.

A series of Nω-nitro-Nω'-substituted guanidines has been prepared as potential inhibitors of the human Nitric Oxide Synthase (NOS) isoforms. The reported utility of aminoguanidine and nitroarginine in iNOS inhibition points to a potential similar utility for analogs of nitro-guanidine. The compound library was tested against the three isoforms of Nitric Oxide Synthase (eNOS, iNOS and nNOS). Sev...

Nitric oxide synthase stabilizes the tetrahydrobiopterin cofactor radical by controlling its protonation state.

Nitric oxide synthase (NOS), a homodimeric enzyme with a flavin reductase domain and a P450-type heme-containing oxygenase domain, catalyzes the formation of NO from L-arginine, NADPH, and O(2) in a two-step reaction sequence. In the first step, a tetrahydrobiopterin (H(4)B) cofactor bound near one of the heme propionate groups acts as an electron donor to the P450-type heme active site, yieldi...

Dexamethasone, tetrahydrobiopterin and uncoupling of endothelial nitric oxide synthase

OBJECTIVE To find out whether dexamethasone induces an uncoupling of the endothelial nitric oxide synthase (eNOS). METHODS & RESULTS A major cause of eNOS uncoupling is a deficiency of its cofactor tetrahydrobiopterin (BH4). Treatment of human EA.hy 926 endothelial cells with dexamethasone decreased mRNA and protein expression of both BH4-synthesizing enzymes: GTP cyclohydrolase I and dihydro...