Reactive Oxygen

Transfer of electrons to oxygen in electron transport by cytochrome oxidase occurs one electron at a time. These kinds of transfers are rarely 100% complete, generating incompletely reduced oxygen species. These oxygen species include superoxide, formed from a one-electron reduction of O 2; hydrogen peroxide (H 2O 2), generated from a two-electron reduction; and hydroxyl radical, formed via a three-electron reduction. In addition, some enzymes, such as xanthine oxidase and amino acid oxidase, generate hydrogen peroxide as ordinary products. Superoxide, hydrogen peroxide, and hydroxyl radical are more reactive than O 2, so they are referred to collectively as reactive oxygen species (ROS).

> Hydroxyl Radical - Hydroxyl radical damages proteins, nucleic acids, and the fatty acids in membrane lipids (lipid peroxidation). Lipid peroxidation occurs as a chain reaction. Hydroxyl radical is produced as a result of ionizing radiation and represents the most active mutagen derived from ionizing radiation. It is also produced from H 2O 2 in the Fenton reaction:

> H 2O 2 + Fe2+ (or Cu+) -> Fe3+ (or Cu2+) + OH radical + OH-

> Superoxide - Superoxide, in and of itself, is relatively nontoxic. It is a free radical, however, so it combines readily with nitric oxide, another free radical that is a biological signaling agent. The product is peroxynitrite (OONO-), which is also considered a ROS. Peroxynitrite causes lipid peroxidation and also causes nitration of tyrosyl hydroxyl groups in proteins, a reaction particularly damaging to membrane proteins.

Large scale production of reactive oxygen species has the potential to inflict considerable damage on the tissues in which they are produced, a situation called oxidative stress. Antioxidant compounds, such as glutathione, vitamin C and vitamin E, and uric acid provide non-enzymatic protection against oxidative stress because they can scavenge ROS before the ROS can cause damage. Alternatively, antioxidant compounds can prevent oxidative damage from spreading, such as the chain reaction of lipid peroxidation. Vitamin E is the principal lipid-soluble antioxidant compound and plays an important role in preventing membrane damage. -Carotene and other carotenoid compounds related to vitamin A are lipid-soluble antioxidants that also play roles in free radical trapping. Glutathione plays an important role in cellular antioxidant protection. Vitamin C (ascorbic acid) is present in far higher amounts in cellular fluids and probably plays the predominant role in extracellular antioxidant protection. A major antioxidant role of uric acid may be its ability to bind and inactivate peroxynitrite.

Enzymatic mechanisms can defend against ROS, too. Superoxide dismutase (SOD) is a family of metalloenzymes that catalyze dismutation (reactions in which identical molecules have different fates). The reaction catalyzed is as follows:

Hydrogen peroxide is metabolized either by catalase or by a more limited family of peroxidases. Catalase catalyzes the following reaction:

> 2H 2O 2 -> 2H 2 O + O 2

Glutathione peroxidase catalyzes reduction of H 2 O 2 as follows:

> 2GSH + H 2 O 2 -> GSSG + 2H 2O

Here GSH is reduced glutathione and GSSG is oxidized glutathione.

Some cells produce ROS as a normal part of their functioning. Certain white blood cells contribute to defense against infectious agents by phagocytosis. Such cells can engulf a bacterial cell, followed by a respiratory burst - a rapid increase in oxygen uptake. Much of the oxygen is reduced to superoxide ion and to H 2O 2, which help to kill the engulfed bacterium.

See also: Oxygen Metabolism and Human Disease, Antioxidants