Nitric oxide (NO) is an essential signaling molecule central to biological processes such as platelet aggregation and adhesion, innate immune response, vasodilation (blood vessel widening), cellular injury and post-translational protein modification (S-nitrosylation) [1]. The mammalian enzyme nitric oxide synthase (NOS) generates NO through an oxidative process using molecular oxygen and arginine as reactants. Without oxygen, NOS is inactive, yet NO is still produced in hypoxic tissues containing high concentrations of nitrite. Biochemical reduction of nitrite to NO (equation (1)) could account for these observations. While bacterial Cu- and heme-dependent nitrite reductase enzymes are well known [2], no known nitrite reductase enzymes are found in plants or animals leading to the hypothesis that they may possess enzymes that ‘moonlight’ as nitrite reductases under hypoxic conditions in addition to their normal function.
NO2− + 2H+ + e− ⇌ NO + H2O (1)
The five eukaryotic Mo-dependent enzymes have all been linked to NO synthesis through nitrite reductase activity [3-8] with NO detection in biological tissues being the primary method of analysis. Given the complexity of this medium and the reactivity of nitrite, consensus is lacking on the relative abilities of these Mo-enzymes to act as nitrite reductases. We have used electrochemistry to examine the activity of Mo enzymes to reduce NO2– to NO under physiologically relevant conditions and our latest results from this investigation will be presented.
Acknowledgments: Support from the Australian Research Council is gratefully acknowledged.
References