Reactive oxygen species

Reactive oxygen species (ROS) - also known as oxygen radicals - are a variety of compounds that are derived from molecular oxygen (O2) but are highly reactive in contrast to molecular oxygen. Due to their chemical aggressiveness, ROS play an important role in inflammatory phenomena and other pathological processes (these reactions are summarized under the term "oxidative stress"). Reactive oxygen species cause protein oxidation in proteins and lipid peroxidation in lipids.

The ROS include free radicals like:

• the hyperoxide anion (old name: superoxide anion) O2-
• the highly reactive hydroxyl radical OH-,
• the peroxyl radical ROO-
• the alkoxyl radical RO- of lipids.

Furthermore, stable molecular oxidants like:

• hydrogen peroxide H2O2
• Hydroperoxide ROOH
• Ozone O3
• Hypochlorite anion OCl-
• Singlet oxygen (O2)

In the organism, reactive oxygen species are formed in the mitochondria. There they are a by-product of cellular respiration. The mitochondrial O2 production is directly proportional to the oxygen tension and is therefore a major factor in oxygen toxicity. Furthermore, reactive O2 is produced by numerous flavin-dependent dehydrogenases (also in plants).

In the context of inflammatory phenomena, phagocytes play the decisive role as a source of reactive O2. In monocytes, macrophages and polymorphonuclear leukocytes, O2 is produced by a membrane-bound NADPH oxidase and released into the extracellular milieu to become effective.

The production of reactive oxygen by phagocytes is normally low. However, it increases excessively by more than tenfold when phagocytes are activated, e.g. during phagocytosis. The radical formation of oxygen by phagocytes clearly serves the defence against infection.

Not only opsonated bacteria, but also a variety of non-infectious foreign bodies as well as endogenous or xenogenic substances can stimulate oxygen production in phagocytes. These include the complement factor C5a, leukotriene B4 and bacterial leukotactic peptides.

ROS (mainly hydrogen peroxide and nitric oxide) are also produced by plants and are used in the defence against numerous pathogens. ROS such as hyperoxide and hydrogen peroxide appear to play an important signaling role, e.g. in the brain during signal transmission.

Organic hydroperoxides: These molecules are formed by auto-oxidation of unsaturated fatty acids in membrane lipids. Such autooxidation processes take place in the organism during any oxidative stress. In this process fatty acid peroxides are formed, for example; these are also unstable and decompose into aldehydes via intermediate stages. Their most important representative is malondialdehyde. This in turn can cross-link proteins.

Myeloperoxidase products: Myeloperoxidase, also known as MPX, an inhibitor protein found in neutrophil granulocytes, combines oxygen peroxide with physiological halides (chloride, iodide) to form reactive acids (e.g. with chloride to form hypochlorous acids). These can react with any biogenic amines (e.g. amino acids).

Reactive nitrogen species: The reaction of the hyperoxide anion O2-- with nitric oxide NO- produces peroxynitrite, ONOO-. This highly reactive radical, together with nitric oxide, is called a "reactive nitrogen species" or RNA.

Inactivation of reactive oxygen species: For this important reaction, the organism has a whole range of metabolic functions at its disposal: superoxide dismutase, catalase, glutathione peroxidase. Alpha-tocopherol is considered to be the antioxidant in the lipophilic environment. Similarly, carotenoids, as polyene derivatives, can scavenge singlet oxygen.