Inducible nitric oxide synthase catalyzes ethanol oxidation to α-hydroxyethyl radical and acetaldehyde

The physiologic function of nitric oxide synthases, independent of the isozyme, is well established, metabolizing l-arginine to l-citrulline and nitric oxide (NO). This enzyme can also transfer electrons to O2, affording superoxide (O2−) and hydrogen peroxide (H2O2). We have demonstrated that NOS1, in the presence of l-arginine, can biotransform ethanol (EtOH) to α-hydroxyethyl radical (CH3CHOH). We now report that a competent NOS2 with l-arginine can, like NOS1, oxidize EtOH to CH3CHOH. Once this free radical is formed, it is metabolized to acetaldehyde as shown by LC-ESI-MS/MS and HPLC analysis. These observations suggest that NOS2 can behave similarly to cytochrome P-450 in the catalysis of acetaldehyde formation from ethanol via the generation of α-hydroxyethyl radical when l-arginine is present.