Electrochemistry of pterin cofactors and inhibitors of nitric oxide synthase

Citation
Acf. Gorren et al., Electrochemistry of pterin cofactors and inhibitors of nitric oxide synthase, NITRIC OXID, 5(2), 2001, pp. 176-186
Citations number
56
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
ISSN journal
1089-8603 → ACNP
Volume
5
Issue
2
Year of publication
2001
Pages
176 - 186
Database
ISI
SICI code
1089-8603(200104)5:2<176:EOPCAI>2.0.ZU;2-Z
Abstract
Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS), but its function is not fully understood. Specifically, it is uncle ar whether BH4 participates directly in electron transfer. We investigated the redox properties of BH4 and several other pteridines with cyclic voltam metry and Osteryoung square wave voltammetry. BH4 was oxidized at a potenti al of +0.27 V vs normal hydrogen electrode (NHE); the corresponding reducti ve signal after the reversal of the scan direction was very small. Instead, reduction occurred at a potential of -0.16 V vs NHE; there was no correspo nding oxidative signal. These two transitions were interdependent, indicati ng that the reductive wave at -0.16 V represented the regeneration of BH4 f rom its product of oxidation at +0.27 V. Similar voltammograms were obtaine d with tetrahydroneopterin and 6,7-dimethyltetrahydropterin, both of which can substitute for BH4 in NOS catalysis. Completely different voltammograms were obtained with 7,8-dihydrobiopterin, sepiapterin, 2'-deoxysepiapterin, and autoxidized BH4. These 7,8-dihydropterins, which do not sustain NOS ca talysis, were oxidized at much higher potentials (+0.82-1.04 V vs NHE), and appreciable reduction did not occur between +1.2 and -0.8 V, in line with the concept of a redox role for BH4 in NOS catalysis. However, the electroc hemical properties of the potent pterin-site NOS inhibitor 4-amino-BH4 rese mbled those of BH4, whereas the active pterin cofactor 5-methyl-BH4 was not re-reduced after oxidation. We conclude that the 2-electron redox cycling of the pterin cofactor between BH4 and quinonoid dihydrobiopterin is not es sential for NO synthesis. The data are consistent with 1-electron redox cyc ling between BH4 and the trihydrobiopterin radical BH3(.). (C) 2001 Academi c Press.