Peroxisome-catalase system

The peroxisome catalase system catalyses the hydrogen peroxide (H2O2 (-dependent oxidation of ethanol to acetaldehyde and water. Normally it contributes little to the oxidation of alcohol because of the limited availability of hydrogen peroxide. However, activation of peroxisomal catalase, by the increased generation of hydrogen peroxide via peroxisomal /3-oxidation, leads to an increased metabolism of alcohol. This state may contribute to an alcohol-related inflammation and necrosis in alcoholic liver disease. 

Peroxisomes are found in many tissues, including liver. They are rich in oxidases and in catalase, Thus, the enzymes that produce H2O2 are grouped with the enzyme that destroys it. However, mitochondrial and microsomal electron transport systems as well as xanthine oxidase must be considered as additional sources of H2O2. 

A modified form of P-oxidation is found in peroxisomes and leads to the formation of acetyl-CoA and H2O2 (from the flavoprotein-linked dehydrogenase step), which is broken down by catalase. Thus, this dehydrogenation in peroxisomes is not linked directly to phosphorylation and the generation of ATP. The system facilitates the oxidation of very long chain fatty acids (eg, Cjq, C22). These enzymes are induced by... 

In summary, substantial progress has been made over the past few years in understanding the cytoplasmic organelle peroxisome and factors that alter its normal functions. Peroxisome proliferator-in-duced increase in the liver peroxisomes is associated with an approximately two-fold increase in catalase activity and several-fold increases in the activity of the peroxisomal fatty acid jS-oxidation system. It is also evident from the available literature that hepatic peroxisomal proliferation appears to be a carcinogenic event in rodents, and this may depend on the potency of the inducer. However, there is no single mechanism that is attributed to the peroxisome proliferation or carcinogenesis induced by... 

Over 90% of alcohol in the plasma is metabolized in the liver by three enzyme systems that operate within the hepatocyte. The remainder is excreted by the lungs and in urine and sweat. Alcohol is metabolized to acetaldehyde by alcohol dehydrogenase in the cell. In turn, acetaldehyde is metabolized to carbon dioxide and water by the enzyme aldehyde dehydrogenase. A second pathway for oxidation of alcohol uses catalase, an enzyme located in the peroxisomes and microsomes. The third enzyme system, the microsomal alcohol oxidase system, has a role in the oxidation of alcohol to acetaldehyde. These last two mechanisms are of lesser importance than the alcohol dehydrogenase-aldehyde dehydrogenase system. 

The import of catalase and other proteins into rat liver peroxisomes can be assayed in a cell-free system similar to that used for monitoring mitochondrial protein Import (see Figure 16-25). By testing various mutant catalase proteins in this system, researchers discovered that the sequence Ser-Lys-Leu (SKL in one-letter code) or a related sequence at the C-terminus was necessary for peroxisomal targeting. Further, addition of the SKL sequence to the C-termlnus of a normally cytosolic protein leads to uptake of the altered protein by peroxisomes in cultured cells. All but a few of the many different peroxisomal matrix proteins bear a sequence of this type, known as peroxisomal-targeting sequence 1, or simply PTSl. 

Human cells have a manganese-containing SOD (Mn-SOD) in the mitochondria, whereas the copper- and zinc-containing SOD (Cu,Zn-SOD) is primarily present in the cytosol [39]. Two enzyme systems exist to catalyze the breakdown of H202. Firstly, the enzyme catalase, which is located in the peroxisomes, converts H202 into H20 and 02 (Eq. 2) [35]. 

Hydrogen peroxide, once formed, mnst be reduced to water to prevent it from forming the hydroxyl radical in the Fenton reaction or Haber-Weiss reactions (see Fig. 24.4) One of the enzymes capable of reducing hydrogen peroxide is catalase (Fig.24.15). Catalase is found principally in peroxisomes, and to a lesser extent in the cytosol and microsomal fraction of the cell. The highest activities are found in tissnes with a high peroxisomal content (kidney and liver). In cells of the immune system, catalase serves to protect the cell against its own respiratory burst. 

Catalase-positive organelles were found to be more numerous in normal than in colonic neoplastic cells (Cable et al. 1992). The specific activities of catalase, fatty-acyl CoA oxidase and enoyl-CoA hydratase/3 hydroxyacyl-CoA dehydrogenase (the so-called peroxisomal bifunctional enzyme of the P-oxidation system) were found to be diminished in carcinoma cells compared with control tissue. 

A list of important chloroplast scavenging systems (in addition to peroxisome-located catalase) is presented in Table 1.1, together with the toxic species that they control. The function of the carotenoid pigments has been outlined already, and the inhibition of their production has severe toxic consequences (see Chapter 4 of this volume). The CuZn chloroplast enzyme superoxide dismutase is the first line of defense against chloroplast... 

During the operation of glycolate oxidase in normal photorespiration, hydrogen peroxide is formed and is removed by peroxisome-based catalase. The potential toxic action of hydrogen peroxide has already been discussed, and the herbicidal action of aminotriazole is assumed to be, in part, due to catalase inhibition.Mutants of barley that are catalase deficient are rapidly bleached in normal air, in which photorespiration may operate, but will grow normally under C02-enriched air. " It is of interest that in this barley mutant and also in aminotriazole-treated plants, there was an enhancement in the level of leaf glutathione, probably due to increased pressure upon radical-scavenging systems. 

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