Abstract
It is well documented that the metabolism of ethanol occurs through a series of pyridine nucleotide-linked enzymatic reactions resulting in the production of acetaldehyde and acetate. The factors regulating hepatic acetaldehyde oxidation are of critical importance, since ethanol-derived acetaldehyde has been implicated in hepatic lipid peroxidation. Isolated hepatocytes incubated in high concentrations of acetaldehyde exhibit significant increases in lipid peroxidation as measured by malondialdehyde formation (Stege, 1982); and the infusion of acetaldehyde to perfused rat liver also stimulates lipid peroxidation as measured by an increased formation of ethane (Muller and Sies, 1983). Recently an alternative pathway of ethanol metabolism has been identified which may also contribute to initiation of hepatic lipid peroxidation (Reinke, et al., 1991; and Knecht et al. 1990). Occurring independent of the pyridine nucleotide-linked dehydrogenase enzymes, this enzymatic pathway involves a P-450 mediated, one electron oxidation of ethanol resulting in the production of an ethanol-derived free radical which could serve as an initiator of lipid peroxidation.
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References
Alin, P., Danielson, U.H., Mannervik, B., 1985, 4-Hydroxyalk-2-enals are substrates for glutathione transferase, FEBS lett., 179. 261.
Cadenas, E., Muller, A., Brigelius, R., Esterbauer, H., Sies, H., 1983, Effects of 4-hydroxynonenal on isolated hepatocytes: studies on chemiluminescence response, alkane production, and glutathione status, Biochem. J., 214: 479.
Esterbauer, H., Zollner, H., Scholz, N., 1975, Reaction of glutathione with conjugated carbonyls, Z. Naturforsch., 30: 466.
Esterbauer, H., Zollner, H., Lang J., 1985, Metabolism of lipid peroxidation product 4-hydroxynonenal by isolated hepatocytes and by liver subcellular fractions, Biochem. J., 228: 363.
Esterbauer, H., Schaur, R.J., Zollner, H., 1991 Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde, and related aldehydes, Free Rad. Biol. Med., 11: 81.
Gornall, A.G., Bardawill, L.J., David, M.M., 1949, Determination of serum proteins by means of a biuret reaction, J. Biol. Chem., 247: 260.
Hellstrom, E., Tottmar, O., 1982, Effects of acetaldehyde dehydrogenase inhibitors on enzymes involved in the metabolism of biogenic aldehydes in rat liver and brain, Biochem. Pharmacol., 31: 3899.
Hjelle, J., Grubbs, J. and Petersen, D.R., 1982, Inhibition of mitochondrial aldehyde dehydrogenase by malondialdehyde, Toxicol. Letters., 41: 436
Ishikawa, T., Esterbauer, H., Sies, H., 1986, Role of cardiac glutathione transferase and of glutathione S-conjugate export system in biotransformation of 4-hydroxynonenal in the heart, J. Biol. Chem., 261: 1576.
Kawase, T., Kato, S., Lieber, C.S., 1989, Lipid peroxidation and antioxidant defense systems in rat liver after chronic ethanol feeding, Hepatology, 10: 815.
Knecht, K.T., Bradford, B.U., Mason, R. P., Thurman, R.G., 1990, In vivo formation of a free radical metabolite of ethanol, Molec. Pharmacol., 38: 26.
Korsten, M.A., Matsuzaki, S., Fieinman, L., Lieber, C.S., 1975, High blood acetaldehyde levels after ethanol administration. Differences between alcoholic and non-alcoholic subjects. N. Engl. J. Med., 292, 386.
Lieber, C.S., 1991, Hepatic, metabolic and toxic effects of ethanol: 1991 update, Alcoholism: Clin. Exp. Res., 15: 573.
Little, R.G., Petersen, D.R., 1983, Subcellular distribution and kinetic parameters of HS mouse liver aldehyde dehydrogenase, Comp. Biochem. Physiol., 74: 271.
Mitchell, D.Y., Petersen, D.R., 1987, The oxidation of α, ß-unsaturated aldehydic products of lipid peroxidation by rat liver aldehyde dehydrogenases, Toxicol. Appl. Pharmacol., 87: 403.
Mitchell, D.Y., Petersen, D.R., 1991, Inhibition of rat hepatic mitochondrial aldehyde dehydrogenase-mediated acetaldehyde oxidation by trans-4-hydroxy-2-nonenal, Hepatology, 13: 728.
Muller, A., Sies, H., 1983, Ethane release during metabolism of aldehydes and monoamines in perfused rat liver, Br. J. Biochem., 134: 599.
Reinke, L.A., Kotake, Y., McCay, P.B., Janzen, E.G., 1991, Spin-trapping studies of hepatic free radicals formed following the acute administration of ethanol to rats: in vivo detection of 1-hydroxyethyl radicals with PBN, Free Rad. Med. Biol., 11: 31.
Reed, D. J., Babson, J.R., Beatty, P.W., Brodie, A.E., Ellis, W.W., Potter, D.W., 1980, Highperformance liquid chromatography analysis of nanomole levels of glutathione, glutathione disulfide, and related thiols and disulfides, Anal. Biochem., 106: 55.
Schaur, R.J., Zollner, H., Esterbauer, H., 1991, Biological effects of aldehydes with particular attention to 4-hydroxynonenal and malonaldehyde, in: “Membrane Lipid Oxidation, Vol. III.,” C. Vigo-Pelfrey, ed., CRC Press, Inc., Boca Raton.
Stege, T.E., 1982, Acetaldehyde-induced lipid peroxidation in isolated hepatocytes, Res. Commun. Chem. Pathol. Pharmacol., 36: 287.
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Hartley, D.P., Petersen, D.R. (1993). Metabolic Interactions of 4-Hydroxynonenal, Acetaldehyde and Glutathione in Isolated Liver Mitochondria. In: Weiner, H., Crabb, D.W., Flynn, T.G. (eds) Enzymology and Molecular Biology of Carbonyl Metabolism 4. Advances in Experimental Medicine and Biology, vol 328. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2904-0_4
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DOI: https://doi.org/10.1007/978-1-4615-2904-0_4
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