Human xanthine oxidase converts nitrite ions into nitric oxide (NO)

In the heart, NOX4 has been identified in ECs, cardiomyocytes, and fibroblasts.

“In the heart, NOX4 has been identified in ECs, cardiomyocytes, and fibroblasts (682, 1058).”

Heart-specific NOX4 overexpression has protective effects in the response to chronic load stress in part due to increased HIF1α response and increased angiogenesis.

“Heart-specific NOX4 overexpression has protective effects in the response to chronic load stress in part due to increased HIF1α response and increased angiogenesis (1058).”

Xanthine oxidoreductase can mediate the one-electron reduction of nitrite to NO under anoxic conditions.

“Despite early studies by Zhang et al [21, 22] and Millar et al [23] demonstrating that xanthine oxidoreductse can mediate the one-electron reduction of nitrite to NO under anoxic conditions”

Nitrite reduction is not exclusive to hemoglobin and myoglobin; a variety of heme-containing and non-heme containing proteins have been suggested as mediators of NO formation.

“Nitrite reduction is not exclusive to hemoglobin and myoglobin, with a variety of heme-containing and non-heme containing proteins including xanthine oxidoreductase [21, 22], aldehyde oxidase [62], neuroglobin [63, 64], eNOS [65], cytochrome c [47], carbonic anhydrase [66], cytochrome c oxidase [67], complex III [68], and cytochrome P450 [69] being suggested as mediators of NO-formation.”

Nitrite reduction to NO involves mechanisms including pH-dependent reduction in the stomach, reduction by xanthine oxidase, deoxyhemoglobin, myoglobin, cytochrome P450, and enzymes of the mitochondrial respiratory chain.

“The mechanisms involved in nitrite reduction to NO include pH-dependent reduction in the stomach [9,10] or reduction by xanthine oxidase [11,12], deoxyhemoglobin [13], myoglobin [14,15], cytochrome P450 [16], and enzymes of the mitochondrial respiratory chain [17].”

Dietary NO3− supplementation elevates nitric oxide bioavailability via reduction of exogenous NO3− to nitrite by commensal anaerobic bacteria in the oral cavity, followed by one-electron reduction of NO2− to NO catalyzed by various NO2− reductases in tissue and blood.

“Dietary NO3− supplementation has been observed to elevate nitric oxide (NO) bioavailability via the reduction of exogenous NO3− to nitrite (NO2−) by commensal anaerobic bacteria in the oral cavity [79], followed by the one-electron reduction of NO2− to NO (and other nitrogen intermediates) catalyzed by various NO2− reductases [80,81,82,83,84] in the tissue and blood.”