Physiological Roles of Xanthine Oxidoreductase

Abstract

Xanthine oxidoreductase (XOR) is a major protein component of the milk fat globule membrane (MFGM) surrounding fat droplets in milk and its enzymology is well characterised. The enzyme is widely distributed in mammalian tissues and is generally accepted to be a key enzyme of purine catabolism. It catalyses the oxidation of a wide range of substrates and can pass electrons to molecular oxygen, generating reactive oxygen species (ROS); similar reduction of nitrite yields reactive nitrogen species (RNS). While XOR has been implicated in ischemia-reperfusion injury, its involvement in normal physiological processes has been less studied. It is argued here that XOR-derived ROS and RNS play a role in innate immunity, specifically in the inflammatory response and in anti-microbial defense of the gastrointestinal tract. XOR-derived species could also be involved in signalling. Additionally, XOR is likely to play a part in metabolism of xenobiotics and has recently been shown to mediate the secretion of milk fat globules. The human enzyme has only relatively recently been characterized. The enzyme purified from breast milk shows very low enzymatic activity, and it is suggested that human XOR has evolved so as to be regulated by an exceptional range of pre- and posttranslational mechanisms.