Nitric Oxide Dioxygenase

Nitric oxide dioxygenase (EC 1.14.12.17) is an enzyme that catalyzes the conversion of nitric oxide (NO) to nitrate (NO−
3) . The net reaction for the reaction catalyzed by nitric oxide dioxygenase is shown below:

• 2NO + 2O₂ + NAD(P)H → 2NO₃- + NAD(P)+ + H+

Nitric oxide is a ubiquitous small molecule that is integrated in a wide variety of physiological processes including smooth muscle vasodilation, platelet disaggregation, neurotransmission, and immune response to bacterial infection. Overproduction of this signaling molecule can be lethal to cells by poisoning cellular energy production. The most sensitive targets of NO are aconitase, an enzyme that catalyzes the isomerization of citrate to isocitrate in the citric acid cycle, and cytochrome oxidase, the last enzyme in the respiratory electron transport chain of mitochondria. Additionally NO, with its lone radical on the nitrogen atom, is implicated in a number of secondary mechanisms of toxicity, including catalase inhibition (resulting in hydrogen peroxide toxicity), Fe-S center iron liberation, and the formation of dinitosyl-iron complexes.

Due to the potential lethality of NO, cells benefitted greatly from the evolution of an enzyme capable of catalyzing the conversion of toxic NO to nitrate. A 'nitric oxide dioxygenase' is an enzyme that is capable of carrying out this reaction. NO dioxygenase belongs to the family of oxidoreductases, more specifically those acting on paired donors, with O₂ as oxidant and with incorporation of two atoms of oxygen into the other donor.