Peroxidation, peroxides peroxisomes

In their review some years ago, Reddy and Rao (1986) cited several lines of evidence for peroxisome-proliferation-mediated oxidative stress being associated with hepatocarcinogenesis. They mentioned the sustained increase in hydrogen peroxide production, the detectable increased levels of hydrogen peroxide in the livers of treated animals, increased lipid peroxidation associated with treatment and marked inhibition of hepatocarcinogenesis by antioxidant compounds. However, definitive studies remain to be carried out. 

IV. Superoxide dismutase (EC 1.15.1.1) Within a cell the superoxide dismutases (SODs) constitute the first line of defense against ROS. Superoxide radical (02) is produced where an electron transport chain is present, as in mitochondria and chloroplasts, but 02 activation may occur in other subcellular locations such as glyoxysomes, peroxisomes, apoplast and the cytosol. Thus SODs are present in all these cellular locations, converting superoxide into hydrogen peroxide and water (i.e. copper/zinc SODs are typically found in the nuclei and cytosol of eukaryotic cells). 

Adrenoleukodystrophy X-linked Peroxisomal membrane protein in the ABC transporter family Decreased peroxidation of saturated, very-long-chain fatty acids, causing their accumulation in brain, adrenals and other tissues variable phenotypes with regard to hypomyelination see text 1,26, Ch. 40... 

Peroxisomes are spherical vesicles bounded by a single membrane. They contain enzymes that catalyse oxidations that produce hydrogen peroxide which is degraded by the enzyme catalase. For example, very long or unusual fatty acids that are present in the diet but have no function are completely degraded in the peroxisomes. 

Enzymes with an intermittent role may be much more important than we thought in 1963. This was perhaps first clearly emphasized by Deis-seroth and Bounce in their catalase review of 1970 (25). These authors also pointed out the likelihood that the specific location of most eukaryotic catalase in the peroxisomes represents a functional response to the need to decompose hydrogen peroxide generated by the aerobic oxidases present in these same organelles, including hydroxy-acid oxidases and D-amino-acid oxidases. 

An alternative form of p-oxidation takes place in hepatic peroxisomes, which are specialized for the degradation of particularly long fatty acids (n > 20). The degradation products are acetyl-CoA and hydrogen peroxide (H2O2), which is detoxified by the catalase (see p. 32) common in peroxisomes. 

Peroxide value (POV), 656, 657-64 chromatography, 672 colorimetric determination, 632 mbber and elastomers, 676 Peroxisomes, antioxidant in biological systems, 610, 611 Peroxo complexes... 

Elliott, B.M. Elcombe, C.R. (1987) Lack of DNA damage or lipid peroxidation measured in vivo in the rat liver following treatment with peroxisomal proliferators. Carcinogenesis, 8, 1213-1218... 

Kombrast, D.J., Barfknecht, T.R. Ingram, P. (1984) Effect of di(2-ethylhexyl)phthalate on DNA repair and lipid peroxidation in rat hepatocytes and on metabolic cooperation in Chinese hamster V-79 cells. J. Toxicol, environ. Health, 13, 99-116 Kurata, Y., Kidachi, F., Yokoyama, M., Toyota, N., Tsuchitani, M. Katoh, M. (1998) Subchronic toxicity of di(2-ethylhexyl)phthalate in common marmosets lack of hepatic peroxisome proliferation, testicular atrophy, or pancreatic acinar cell hyperplasia. Toxicol. Sci., 42, 49-56... 

Chronic administration of peroxisome proliferators to rodents results in sustained oxidative stress due to overproduction of peroxisomal hydrogen peroxide. The induction of peroxisomal fatty acid P-oxidation by cinnamyl anthranilate in vivo under bioassay conditions (Lake et al, 1997) supports this h othesis. Other data on the induction of oxidative stress are not available for cinnamyl anthranilate. 

Catalase A haem-based enzyme which catalyzes the decomposition of hydrogen peroxide into oxygen and water. It is found e.g. in peroxisome located in the liver. 

Acyl CoA oxidase, which is induced up to at least 15 X normal levels, catalyzes a specific step characteristic of jl-oxidation in the peroxisome-producing hydrogen peroxide as a byproduct (Fig. 7.10). Other oxidases may also lead to increased hydrogen peroxide. Normally, this is removed and detoxified by the enzyme catalase, which breaks hydrogen peroxide down to water and oxygen. However, catalase is only increased about twofold after treatment with peroxisomal proliferators. 

Thus, as previously discussed, hydroxyl radical can initiate lipid peroxidation, generating free radicals as well as directly damaging DNA. Oxidative damage to proteins yields lipofuscin, which is known to accumulate in rodent liver treated with peroxisomal proliferators. Treatment with antioxidants will inhibit the liver cancer. 

Figure 7.10 Part of the peroxisomal 3-oxidation pathway showing the production of hydrogen peroxide by acyl CoA oxidase. Hydrogen peroxide can be detoxified by catalase to water and oxygen. However, in the absence of sufficient enzyme, it can be broken down to the highly reactive hydroxyl radical in the presence of metal ions such...

Tamura, H.. lida. T.. Watanabe, T. Suga, T. (1990) Long-term effects of hypolipidemic peroxisome proliferator administration on hepatic hydrogen peroxide metabolism in rats. Carcinogenesis, 11,445-450... 

Peroxisomes are rich in enzymes that produce and decompose hydrogen peroxide. They often make a major contribution to the oxidative metabolism of cells. In germinating oilseeds glyoxysomes, a type of peroxisome, contain enzymes that catalyze reactions of the biosynthetic "glyoxylate pathway" of metabolism.51 Organelles that resemble peroxisomes in appearance... 

Peroxisomes contain enzymes involved in the breakdown of amino acids and fatty acids, a byproduct of which is hydrogen peroxide. This toxic compound is rapidly degraded by the enzyme catalase, also found within the peroxisomes. 

These organelles have a single boundary membrane and contain enzymes that degrade fatty acids and amino acids. A byproduct of these reactions is hydrogen peroxide, which is toxic to the cell. The presence of large amounts of the enzyme catalase in the peroxisomes rapidly converts the toxic hydrogen peroxide into harmless HzO and 02 ... 

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