Organelle glutathione

Organelle Glutathione Protection Against Oxidative Stress... 

Haloalkanes. Certain haloalkanes and haloalkane-containing mixtures have been demonstrated to potentiate carbon tetrachloride hepatotoxicity. Pretreatment of rats with trichloroethylene (TCE) enhanced carbon tetrachloride-induced hepatotoxicity, and a mixture of nontoxic doses of TCE and carbon tetrachloride elicited moderate to severe liver injury (Pessayre et al. 1982). The researchers believed that the interaction was mediated by TCE itself rather than its metabolites. TCE can also potentiate hepatic damage produced by low (10 ppm) concentrations of carbon tetrachloride in ethanol pretreated rats (Ikatsu and Nakajima 1992). Acetone was a more potent potentiator of carbon tetrachloride hepatotoxicity than was TCE, and acetone pretreatment also enhanced the hepatotoxic response of rats to a TCE-carbon tetrachloride mixture (Charbonneau et al. 1986). The potentiating action of acetone may involve not only increased metabolic activation of TCE and/or carbon tetrachloride, but also possible alteration of the integrity of organelle membranes. Carbon tetrachloride-induced liver necrosis and lipid peroxidation in the rat has been reported to be potentiated by 1,2- dichloroethane in an interaction that does not involve depletion of reduced liver glutathione, and that is prevented by vitamin E (Aragno et al. 1992). 

The chemical is removed before it can properly reach the cytoplasm or important organelles. The substrates for this transporter are structurally diverse but tend to be organic, weakly basic (cationic), or uncharged hydrophobic or amphipathic substances. Thus, the chemical diffuses into the cell and is then pumped out. Substrates include anions conjugated with glutathione (GSH), glucuronic acid, and sulfate. 

Copper The daily intake from food is 0.8—2.0 mg it is released into the portal vein via copper-transporting ATPase. The transport of copper, which is toxic in its free form, is effected by the binding to ceruloplasmin, albumin and transcuprin. Copper is bound to reduced glutathione and metallothionein in the hepatocytes and distributed to various organelles or incorporated into enzymes. The biological effects of copper are manifold and essential for some cellular functions, (s. p. 50) Copper is toxic not only in its free form, but also in cases of overload (e. g. cirrhosis in childhood due to the consumption of water from copper pipes). Copper homoe-ostasis is regulated via biliary excretion (normal value about 1.2-2.0 mg/day), so that the normal value in serum is 75-130 fg/dl. (321, 323, 370, 383, 386) (s. p. 102)... 

A number of these enzymes are expressed in other tissues as well but cause a notable deficiency predominantly in red blood cells because of the life span of the erythrocyte after the loss of protein synthesis. Once an enzyme is degraded or otherwise becomes nonfunctional, it cannot be replaced by new or other compensating proteins because of the lack of nucleus, mitochondria, ribosomes, and other cell organelles in mature red cells. Disorders have been described in the EMP, HMP, Rapoport-Luebering cycle, the glutathione pathway (Figure 21-9), purine-pyrimidine metabolism and methemoglobin reduction. 

Morgenstern, R., Lundqvist, G., Andersson, G., Balk, L., and DePierre, J. W. (1984) The distribution of microsomal glutathione transferase among different organelles, different organs, and different organisms. Biochem. Pharmacol. 33, 3609-3614. 

The term antioxidant refers to a substance which can significantly prevent, stop and/or delay the oxidation of the oxidizable materials as well as cellular organelles via prevention and/or inhibition of chain reactions [25, 26]. In living systems, there is a multiple range of antioxidants such as different antioxidant enzymes (such as catalase, superoxide dismutase, glutathione peroxidases, etc.) as well as non-enzymatic antioxidants (such as glutathione, L-ascorbic acid, a-tocopherol, etc.) [27-29]. However, insufficient antioxidant defense systems... 

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