- Tytuł:
- Single-electron reduction of quinone and nitroaromatic xenobiotics by recombinant rat neuronal nitric oxide synthase
- Autorzy:
-
Anusevičius, Žilvinas
Nivinskas, Henrikas
Šarlauskas, Jonas
Sari, Marie-Agnes
Boucher, Jean-Luc
Čėnas, Narimantas - Powiązania:
- https://bibliotekanauki.pl/articles/1039577.pdf
- Data publikacji:
- 2013
- Wydawca:
- Polskie Towarzystwo Biochemiczne
- Tematy:
-
antitumour agents
nitroaromatic compounds
electron transfer mechanism
oxidative stress
quinones
Neuronal nitric oxide synthase (nNOS) - Opis:
- We examined the kinetics of single-electron reduction of a large number of structurally diverse quinones and nitroaromatic compounds, including a number of antitumour and antiparasitic drugs, and nitroaromatic explosives by recombinant rat neuronal nitric oxide synthase (nNOS, EC 1.14.13.39), aiming to characterize the role of nNOS in the oxidative stress-type cytotoxicity of the above compounds. The steady-state second-order rate constants (kcat/Km) of reduction of the quinones and nitroaromatics varied from 102 M-1s-1 to 106 M-1s-1, and increased with an increase in their single-electron reduction potentials (E17). The presence of Ca2+/calmodulin enhanced the reactivity of nNOS. These reactions were consistent with an 'outer sphere' electron-transfer mechanism, considering the FMNH./FMNH2 couple of nNOS as the most reactive reduced enzyme form. An analysis of the reactions of nNOS within the 'outer sphere' electron-transfer mechanism gave the approximate values of the distance of electron transfer, 0.39-0.47 nm, which are consistent with the crystal structure of the reductase domain of nNOS. On the other hand, at low oxygen concentrations ([O2] = 40-50 μM), nNOS performs a net two-electron reduction of quinones and nitroaromatics. This implies that NOS may in part be responsible for the bioreductive alkylation by two-electron reduced forms of antitumour aziridinyl-substituted quinones under a modest hypoxia.
- Źródło:
-
Acta Biochimica Polonica; 2013, 60, 2; 217-222
0001-527X - Pojawia się w:
- Acta Biochimica Polonica
- Dostawca treści:
- Biblioteka Nauki
Artykuł