Kinetics of nitrite reduction and peroxynitrite formation by ferrous heme in human cystathionine β-synthase
- Autor(es):
- Carballal, S. ; Cuevasanta, Ernesto ; Yadav, P. K. ; Gherasim, C. ; Ballou, D. P. ; Álvarez, Beatriz ; Banerjee, Ruma
- Tipo:
- Artículo
- Versión:
- Publicado
- Resumen:
-
Cystathionine β-synthase (CBS) is a pyridoxal phosphate-dependent enzyme that catalyzes the condensation of homocysteine with serine or with cysteine to form cystathionine and either water or hydrogen sulfide, respectively. Human CBS possesses a noncatalytic heme cofactor with cysteine and histidine as ligands, which in its oxidized state is relatively unreactive. Ferric CBS (Fe(III)-CBS) can be reduced by strong chemical and biochemical reductants to Fe(II)-CBS, which can bind carbon monoxide (CO) or nitric oxide (NO·), leading to inactive enzyme. Alternatively, Fe(II)-CBS can be reoxidized by O2 to Fe(III)-CBS, forming superoxide radical anion (O2 -·). In this study, we describe the kinetics of nitrite (NO2·-) reduction by Fe(II)-CBS to form Fe(II)NO·-CBS. The second order rate constant for the reaction of Fe(II)-CBS with nitrite was obtained at low dithionite concentrations. Reoxidation of Fe(II)NO·-CBS by O2 showed complex kinetic behavior and led to peroxynitrite (ONOO-) formation, which was detected using the fluorescent probe, coumarin boronic acid. Thus, in addition to being a potential source of superoxide radical, CBS constitutes a previously unrecognized source of NO· and peroxynitrite.
- Año:
- 2016
- Idioma:
- Inglés
- Temas:
- Heme
kinetics
Nitric oxide
Oxygen radicals
Superoxide ion
Hemeprotein
Nitrite
Oxygen
Peroxynitrite
- Institución:
- Universidad de la República
- Repositorio:
- COLIBRI
- Enlace(s):
- https://hdl.handle.net/20.500.12008/22046
- Nivel de acceso:
- Acceso abierto