The interaction of nitric oxide, NO, with heme enzymes and proteins is of wide importance in human health and disease; much less studied is its reduced congener HNO, commonly termed nitroxyl or nitrosyl hydride. Previous work has shown that free HNO is readily trapped by O2-binding proteins like deoxymyoglobin and hemoglobin. We hypothesized that HNO may inhibit or turnover oxygenases in the absence of O2. Indeed, HNO can replace O2 in the activity of a Mn nonheme oxygenase, Quercetin Dioxygenase (QDO), producing unique N-containing products. Nonenzymatic turnover is also observed at high pH, consistent with reactivity of HNO with deprotonated quercetin, suggesting that the enzymatic reactivity may proceed by metal-promoted ionization of the substrate. But in examinations of several different metal-substituted QDO preparations, only the Mn(II) enzyme shows nitroxygenase activity, consistent with a metal-mediated reactivity. We are examining both the enzymatic and non-enzymatic reactivity with a series of substrate analogues to address this issue. We predict that substitution of HNO for O2 may allow a unique approach to studying the mechanism of non-heme oxygenases.

HNO replaces O<sub>2</sub> in turnover of a nonheme Mn dioxygenase: Substrate analog investigations of nitroxygenase activity

244th National Meeting (2012)

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HNO replaces O2 in turnover of a nonheme Mn dioxygenase: Substrate analog investigations of nitroxygenase activity

HNO replaces O₂ in turnover of a nonheme Mn dioxygenase: Substrate analog investigations of nitroxygenase activity