Oxidative stress and disease
By : fh4djh4r
Oxidative stress is a major factor in health, aging, and disease and is often defined by the redox balance established by cellular oxidants and antioxidants. The ratio of reduced to oxidized levels of major low-molecular weight protein thiols, such as cysteine and glutathione or thioredoxin and glutaredoxin, is often used as a measure of oxidative stress. Among naturally occurring thiols, the discovery of a-lipoic acid has led to an unprecedented interest in basic research because of its role in energy metabolism and as an antioxidant for the treatment of certain
diseases. a-Lipoic acid has acquired importance because of its role as a coenzyme in the maintenance of energy metabolism, on one hand, and as an antioxidant and cell redox modulator, on the other hand. The former was supported by the discovery of the essential role of lipoic acid in mitochondrial dehydrogenasedriven reactions inherent in energy metabolism and the latter is supported by reduction of supplemental a-lipoic acid to dihydrolipoic acid in mammalian cells conferring further antioxidant protection. For example, lipoic acid is an essential cofactor of a-keto acid dehydrogenase complexes in eukaryotic cells as part of the lipoyl domain of the E2 enzymes (dihydrolipoamide acyltransferases). Also, exogenous R- (or RS)-lipoic acid is reduced by a flavoenzyme, dihydrolipoamide dehydrogenase, of the complex in mitochondria. Hence lipoic acid may be a mitochondrial-targeted nutrient. The cell redox status is a critical factor regulating cell proliferation, differentiation, apoptosis (programmed cell death), and necrosis, and the mitochondrion is a center of interest for its role in the generation of signaling molecules (e.g., hydrogen peroxide and nitric oxide) that, in turn, modulates the redox status of the cell.
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