TY - JOUR
T1 - The role of tetrahydrobiopterin in the regulation of neuronal nitric-oxide synthase-generated superoxide
AU - Rosen, Gerald M.
AU - Tsai, Pei
AU - Weaver, John
AU - Porasuphatana, Supatra
AU - Roman, Linda J.
AU - Starkov, Anatoly A.
AU - Fiskum, Gary
AU - Pou, Sovitj
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/10/25
Y1 - 2002/10/25
N2 - Tetrahydrobiopterin (H4B) is a critical element in the nitric-oxide synthase (NOS) metabolism of L-arginine to L-citrulline and NO.. It has been hypothesized that in the absence of or under nonsaturating levels of L-arginine where O2 reduction is the primary outcome of NOS activation, H4B promotes the generation of H2O2 at the expense of O2._. The experiments were designed to test this hypothesis. To test this theory, two different enzyme preparations, H4B-bound NOS I and H4B-free NOS I, were used. Initial rates of NADPH turnover and O2 utilization were found to be considerably greater in the H4B-bound NOS I preparation than in the H4B-free NOS I preparation. In contrast, the initial generation of O2.- from the H4B-free NOS I preparation was found to be substantially greater than that measured using the H4B-bound NOS I preparation. Finally, by spin trapping nearly all of the NOS I produced O2.-, we found that the initial rate of H2O2 production by H4B-bound NOS I was considerably greater than that for H4B-free NOS I.
AB - Tetrahydrobiopterin (H4B) is a critical element in the nitric-oxide synthase (NOS) metabolism of L-arginine to L-citrulline and NO.. It has been hypothesized that in the absence of or under nonsaturating levels of L-arginine where O2 reduction is the primary outcome of NOS activation, H4B promotes the generation of H2O2 at the expense of O2._. The experiments were designed to test this hypothesis. To test this theory, two different enzyme preparations, H4B-bound NOS I and H4B-free NOS I, were used. Initial rates of NADPH turnover and O2 utilization were found to be considerably greater in the H4B-bound NOS I preparation than in the H4B-free NOS I preparation. In contrast, the initial generation of O2.- from the H4B-free NOS I preparation was found to be substantially greater than that measured using the H4B-bound NOS I preparation. Finally, by spin trapping nearly all of the NOS I produced O2.-, we found that the initial rate of H2O2 production by H4B-bound NOS I was considerably greater than that for H4B-free NOS I.
UR - http://www.scopus.com/inward/record.url?scp=0037174812&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037174812&partnerID=8YFLogxK
U2 - 10.1074/jbc.M200853200
DO - 10.1074/jbc.M200853200
M3 - Article
C2 - 12183447
AN - SCOPUS:0037174812
VL - 277
SP - 40275
EP - 40280
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 43
ER -