P41. Sulfite oxidase: A novel nitrite reductase that generates nitric oxide

摘要

In the past two decades, two mammalian pterin-based molybdenum (MPT) enzymes, xanthine oxidoreductase (XOR) and aldehyde oxidase (AO), have been shown to exhibit hypoxia-dependent nitrite (NO~-_2) reductase and nitric oxide (NO) generating activity. These findings were recently confirmed in animal models where O_2 and pH-dependent XOR-mediated NO~-_2 reduction in the heart, liver and vasculature was found to modulate physiological and therapeutic responses to nitrite. While XOR is highly expressed in rodents, its enzymatic activity is ~1000-fold lower in humans, which poses the question of relevance as a source of nitrite-mediated NO formation in humans. Moreover, human studies examining nitrite-dependent vasodilation clearly show that this process cannot be blocked by the XO inhibitor oxypurinol. We therefore initiated studies evaluating a third member of the mammalian MPT enzyme family, sulfite oxidase (SO), for NO~-_2 reductase activity.