Free radicals cellular sources

Mandrup-Poulsen, T., Corbett, J. A., McDaniel, M. L., and Nerup, J. (1993). What are the types and cellular sources of free radicals in the pathogenesis of type 1 (insulin-dependent) diabetes mellitus Diabetologia 36, 470-471. 

Vitamin E has been shown, in a wide range of studies, to be capable of affording considerable protection to cells exposed to free radical attack, either from pathological or drug-induced sources. In injured nervous tissue, vitamin E probably exerts its protective effect by scavenging free radicals, stabilizing cellular membranes and quenching the cascade of biochemical events that... 

Mitochondria are the main source of free radicals in the cell and, in turn, ROS can cause inhibition of complex enzymes in the electron transport chain of the mitochondria leading to the shutdown of energy production and amplifying generation of mitochondrial free radicals (Orrenius, 2007). Free radicals can then cause extensive cellular damage by causing oxidation of lipids, proteins, and DNA. 

Although research in this area has been conducted for more than 40 yr, the mechanisms of cerebral protection by mild hypothermia remain unclear and are still a source of controversy. Proposed mechanisms of neuroprotection by mild hypothermia include suppression of neurotransmitter release (2,3), reduced free radical production (4), activity of protein kinases (5), resynthesis of cellular repair proteins (6),... 

Since the primary source of oxygen species (ROS) is the superoxide radical anion O [1] and the most reactive free radical is the hydroxyl radical (HO") a wide spectrum of various oxidants damage the cellular components. The hydroxyl radical, for example, reacts very quickly with all major components of cells, e.g., proteins, hydrocarbons, nucleic acids, and hpids [ 1 ]. 

Mitochondria were classically considered as the subcellular organelles of eukaryotic cells that produce the energy required to drive the endergonic biochemical processes of cell life. Such a concept is now complemented by the consideration of mitochondria as the most important cellular source of free radicals, as the main target for free radical regulatory and toxic actions, and as the source of signaling molecules that command cell cycle, proliferation, and apoptosis. 

The respiratory chain is the major source of oxygen free radicals. In theory, molecular oxygen should be completely reduced in complex IV by four electrons from water without the formation of intermediates. In practice, sometimes partial reduction occurs with oxygen being converted to superoxide anion radicals (Fig. 15.1). Also, the ubiquinone reactions in complexes I and II have an unfortunate tendency to leak electrons directly to oxygen. Overall, up to 2% of cellular oxygen forms superoxide free radicals and the body has developed defence mechanisms to counter their damaging effects. 

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