A new route to peroxynitrite: a role for xanthine oxidoreductase

Abstract

Peroxynitrite, a potent oxidising, nitrating and hydroxylating agent, results from the reaction of nitric oxide with superoxide. We show that peroxynitrite can be produced by the action of a single enzyme, xanthine oxidoreductase (XOR), in the presence of inorganic nitrite, molecular oxygen and a reducing agent, such as pterin. The effects of oxygen concentration on peroxynitrite production have been examined. The physiologically predominant dehydrogenase form of the enzyme is more effective than the oxidase form under aerobic conditions. It is proposed that XOR-derived peroxynitrite fulfils a bactericidal role in milk and in the digestive tract. ß

NADH oxidase activity of rat and human liver xanthine oxidoreductase: potential role in superoxide production

“…Therefore, following the same reasoning as Godberg et al [19], in the presence of oxygen, the XD form will have fewer electrons available for the reduction of nitrite than will XO, and it will generate less ONOO -. This condition is more consistent with the likely role of the predominant in vivo XD form in physiological function.…”

“…Moreover, a new XOR-dependent route for the generation of peroxynitrite, a strong inflammatory oxidant, was described [19]. Both • NO and O 2…”

“…Their overproduction, however, can play a major role in several pathological conditions [12][13][14][15][16]. Moreover, it was recently shown that XOR can catalyse the reduction of nitrates and nitrites, giving rise to both • NO [17,18] and peroxynitrite (ONOO -) [19]. This fact further amplifies the physiological and pathological significance of XOR.…”

“…•- [21], can be produced solely by the action of XOR [19]. The XORderived ONOO -has been proposed as a bactericidal agent in milk and the digestive tract [19].…”

“…The XORderived ONOO -has been proposed as a bactericidal agent in milk and the digestive tract [19].…”