|MadSci Network: Biochemistry|
In 1965 De Duve et al isolated a group of intracellular particles from liver cells and other tissues by using cell fractionation methods. These particles were enriched with some oxidative enzymes, such as peroxidase, catalase, D-amino oxidase, and urate oxidase. The name peroxisome was applied because this organelle is specifically involved in the formation and decomposition of hydrogen peroxide (H2O2). H2O2 and free radicals are produced as a result of certain oxidative reactions involved in the break down of amino acids and fats. These are very reactive chemical species that could damage cellular machinery. To protect the cell from these destructive byproducts, such reactions are segregated within these small membrane-bounded peroxisomes. Peroxisomes contain four enzymes related to the metabolism of H2O2. Three of them - urate oxidase, D-amino oxidase, and alpha-hydroxylic acid oxidase - produce peroxide (H2O2), and catalase destroys it (2H2O2 - 2H2O + O2). Catalase is in the matrix of liver peroxisomes and represents up to 40% of the total protein. The enzyme urate oxidase and two other enzymes present in amphibian and avian peroxisomes are related to the catabolism of purines. catalase is synthesized on free ribosomes, and they are packaged into peroxisomes without undergoing a proteolytic processing. Free radicals are molecules that, because they contain an unpaired electron, are extremely reactive. These include the superoxide radical O2.- (the dot identifies the unpaired electron) and the reactive hydroxyl radical (OH.). H2O2 although not itself a free radical, forms reactive compounds in reactions that are catalyzed by Fe++ and Fe+++. H2O2 also reacts with the superoxide radical to produce even more reactive free radicals. H2O2, as well as superoxide anion (O2.-) are normal metabolites in aerobic cells. The peroxisome is the main source of H2O2; however, only a fraction of this H2O2 diffuses to the cytosol, and most of it is degraded by the intraorganellar catalase. Most Cytoplasmic H2O2 is produced by mitochondria and membranes of the endoplasmic reticulum, although there are also H2O2-producing enzymes in the cytoplasmic matrix. Catalase acts as a "safety valve" for dealing with the large amounts of H2O2 generated by peroxisomes, however, other enzymes such as glutathione peroxidase, are capable of metabolizing hydroperoxides and also H2O2, in the cytosol and mitochondria. The production of superoxide anion in mitochondria and cytosol is regulated mailnly by the enzyme superoxide dismutase. All of these protective enzymes are present in high levels in aerobic tissues. In recent years the possible relationship between peroxides and free radicals (such as O2.-), with the process of aging is being emphasized. Such radicals acting on DNA could produce mutations, altering the transcrition into mRNA and the translation into proteins. In addition free radicals can affect the membranes by causing peroxidation of lipids and proteins. For these reasons reducing compouns such as vitamin E or enzymes like superoxide dismutase couls also play a role in keeping the healthy state of a cell.
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