Figure 1. Production and Metabolism of Reactive Oxygen Species.

Normally over 95% of the oxygen consumed in the body is converted to water by acquisition of 2 electrons in a single step. However, for the remaining 5% this process occurs with the transfer of one electron at a time, leading to formation highly reactive and short-lived species, collectively referred to as ROS. The primary ROS produced in the body is superoxide which is formed from single electron reduction of molecular oxygen. The primary sources of superoxide include the mitochondria, endoplasmic reticulum, cyclooxygenase, lipoxygenase, uncoupled nitric oxide synthase (NOS), NAD(P)H oxidase, xanthine oxidase, and cytochrome P450. Antioxidants then act on ROS to generate less reactive species. For example, superoxide dismutase (SOD) converts superoxide into hydrogen peroxide, which is then reduced by catalase (CAT) into water and oxygen and by glutathione peroxidase (GPX) into water and oxidized glutathione. However in pathological states hydrogen peroxide serves as the substrate for formation of highly reactive and cytotoxic oxidants such as hydroxyl radical by catalytically-active iron (Fe²⁺) and hypochlorous acid by myeloperoxidase. An increase in ROS generation or decrease in antioxidant availability leads to oxidative stress and induction of the pro-inflammatory response, which contribute to disease pathogenesis.