Abstract
Considerable evidence is currently available which strongly suggests that, in addition to the alcohol dehydrogenase (ADH)-catalyzed reaction, a pyrazole-insensitive pathway participates in the metabolism of ethanol in vivo (Israel et al., 1970; Lieber and DeCarli, 1972), in the isolated perfused rat liver (Papenberg et al., 1970; Thurman and McKenna, 1974), in rat and mouse liver slices (Thieden, 1971; Lieber and DeCarli, 1970; Vatsis and Schulman, 1973a; Vatsis et al., 1973), and in isolated rat liver parenchymal cells (Grunnet et al., 1973). The non-ADH pathway has two distinguishing properties, namely, it becomes increasingly important at ethanol concentrations (20–80 mM) well above the Km of AHD (Thieden, 1971; Vatsis et al., 1973; Lieber and DeCarli, 1973), and appears to be inducible by chronic ethanol feeding (Lieber and DeCarli, 1970, 1972) as well as by treatment of animals with phenobarbital (Carter and Isselbacher, 1971; Khanna et al., 1972; Vatsis and Schulman, 1974).
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References
Barakat, H. A., Tapscott, E., and Pennington, S. 1974. Ethanol oxidation by components of rat liver microsomes. Biochem. Biophys. Res. Commun. 60: 482–488.
Baudhuin, P., Beaufay, H., Rahman-Li, Y., Sellinger, O. F., Wattiaux, R., Jacques, P., and DeDuve, C. 1964. Tissue fractionation studies. Intracellular distribution of monoamine oxidase, aspartate aminotransferase, alanine aminotransferase, D-amino acid oxidase and catalase in rat liver tissue. Biochem. J. 92: 179–184.
Carter, E. A., and Isselbacher, K. J. 1971. The role of microsomes in the hepatic metabolism of ethanol. Ann. N. Y. Acad. Sci. 179: 282–294.
Castro, J. A., Greene, F. E., Gigon, P., Sasame, H. and Gillette, J. R, 1970. Effect of adrenalectomy and cortisone administration on components of the liver microsomal mixed function oxygenase system of male rats which catalyzes ethylmorphine metabolism. Biochem. Pharmacol. 19: 2461–2467.
Davies, D. S., Gigon, P. L., and Gillette, J. R. 1969. Species and sex differences in electron transport systems in liver microsomes and their relationship to ethylmorphine demethyla-tion. Life Sci. 8: 85–91.
Deckert, F. W. and Remmer, H. K. 1972. In vitro inhibition of rat and human liver microsomal enzymes by 4-hydroxycoumarin anticoagulants and related compounds. Chem-Biol. Interactions 5: 255–263.
Gigon, P. L., Gram, T. E. and Gillette, J. R. 1969. Studies on the rate of reduction of hepatic microsomal cytochrome P-450 by reduced nicotinamide adenine dinucleotide phosphate; Effect of drug substrates. Mol. Pharmacol. 5: 109–122.
Grunnet, N., Quistorff, B. and Thieden, H. I. D. 1973. Ratelimiting factors in ethanol oxidation by isolated rat-liver parenchymal cells. Effect of ethanol concentration, fructose, pyruvate and pyrazole. Eur. J. Biochem. 40: 275–282.
Hochstein, P. and Ernster, L. 1963. ADP-activated lipid peroxidation coupled to the TPNH oxidase system of microsomes. Biochem. Biophys. Res. Commun. 12: 388–394.
Israel, Y., Khanna, J. and Lin, R. 1970. Effect of 2,4-dinitrophenol on the rate of ethanol elimination in the rat in vivo. Biochem. J. 120: 447–448.
Kato, R. and Takanaka, A. 1968. Metabolism of drugs in old rats. I. Activities of NADPH-linked electron transport and drugmetabolizing enzyme systems in liver microsomes of old rats. Jap. J. Pharmacol. 18: 381–388.
Kato, R., Takanaka, A. and Onoda, K-I. 1970. Studies on age difference in mice for the activity of drug-metabolizing enzymes of liver microsomes. Jap. J. Pharmacol. 20: 572–576.
Khanna, J. M., Kalant, H. and Lin, G. 1970. Metabolism of ethanol by rat liver microsomal enzymes. Biochem. Pharmacol. 19: 2493–2499.
Khanna, J. M., Kalant, H. and Lin, G. 1972. Significance in vivo of the increase in microsomal ethanol-oxidizing system after chronic administration of ethanol, phenobarbital and chlorcyclizine. Biochem. Pharmacol. 21: 2215–2226.
Levin, W., Lu, A. Y. H., Jacobson, M., Kuntzman, R., Poyer, J. L. and McCay, P. B. 1973. Lipid peroxidation and the degradation of cytochrome P-450 heme. Arch. Biochem. Biophys. 158: 842–852.
Lieber, C. S. and DeCarli, L. M. 1970. Hepatic microsomal ethanoloxidizing system. In vitro characteristics and adaptive properties in vivo. J. Biol. Chem. 245: 2505–2512.
Lieber, C. S. and DeCarli, L. M. 1972. The role of the hepatic microsomal ethanol oxidizing system (MEOS) for ethanol metabolism in vivo. J. Pharmacol. Exper. Therap. 181: 279–287.
Lieber, C. S. and DeCarli, L. M. 1973. The significance and characterization of hepatic microsomal ethanol oxidation in the liver. Drug.Metabol. Disp. 1: 428–440.
Lin, G., Kalant, H. and Khanna, J. M. 1972. Catalase involvement in microsomal ethanol-oxidizing system. Biochem. Pharmacol. 21: 3305–3308.
Masters, B. S. S., Kamin, H., Gibson, Q. H. and Williams, C. H. 1965. Studies on the mechanism of microsomal triphosphopyri-dine nucleotide-cytochrome c reductase. J. Biol. Chem. 240: 921–931.
May, H. E., and McCay, P. B. 1968. Reduced triphosphopyridine nucleotide oxidase-catalyzed alterations of membrane phospholipids. II. Enzymic properties and stoichiometry. J. Biol. Chem. 243: 2296–2305.
Mezey, E., Potter, J. J. and Reed, W. D. 1973. Ethanol oxidation by a component of liver microsomes rich in cytochrome P-450. J. Biol. Chem. 248: 1183–1187.
Nash, T. 1953. The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem. J. 55: 416–421.
Nelson, E. B., Kohl, K. B. and Masters, B. S. S. 1973. The role of the NADPH-cytochrome c reductase in the microsomal oxidation of ethanol and methanol. Drug Metabol. Disp. 1: 455–458.
Omura, T. and Sato, R. 1964. The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J. Biol. Chem. 239: 2370–2378.
Ottolenghi, A. 1959. Interaction of ascorbic acid and mitochondrial lipides. Arch. Biochem. Biophys. 79: 355–363.
Papenberg, J., Wartburg, J. P. and Aebi, H. 1970. Metabolism of ethanol and fructose in the perfused rat liver. Enzym. Biol. Clin. 11: 237–250.
Pennington, S. N., Chattopadhyay, S. K. and Brown, H. D. 1970. A possible pathway for ethanol-induced fatty liver and modification of liver injury by antioxidants. Quart. J. Stud. Alc. 31:13–19.
Roach, M. K., Reese, W. N. and Creaven, P. J. 1969. Ethanol oxidation in the microsomal fraction of rat liver. Biochem. Biophys. Res. Commun. 36: 596–602.
Rubin, E., Gang, H., Misra, P. and Lieber, C. S. 1970. Inhibition of drug metabolism by acute ethanol intoxication. A hepatic microsomal mechanism. Am. J. Med. 49: 801–806.
Schacter, B. A., Marver, H. S. and Myer, U. A. 1972. Hemoprotein Catabolism during Stimulation of Microsomal Lipid Peroxidation. Biochim. Biophys. Acta. 279: 221–227.
Teschke, R., Hasumura, Y., Joly, J-G., Ishii, H. and Lieber, C. S. 1972. Microsomal ethanol-oxidizing system (MEOS): Purification and properties of a rat liver system free of catalase and alcohol dehydrogenase. Biochem. Biophys. Res. Commun. 49: 1187–1193.
Teschke, R., Hasumura, Y. and Lieber, C. S. 1974. Hepatic microsomal ethanol-oxidizing system: Solubilization, isolation, and characterization. Arch. Biochem. Biophys. 163: 404–415.
Thieden, H. I. D. 1971. The effect of ethanol concentration on ethanol oxidation rate in rat liver slices. Acta Chem. Scand. 25: 3421–3427.
Thurman, R. B., and McKenna, W. 1974. Activation of ethanol utilization in perfused liver from normal and ethanol-pretreated rats. Hoppe-Seyler’s Z. Physiol. Chem. 355: 336–340.
Thurman, R. G. and Scholz, R. 1973. The role of hydrogen peroxide and catalase in hepatic microsomal ethanol oxidation. Drug Metabol. Disp. 1: 441–448.
Thurman, R. G., Ley, H. G. and Scholz, R. 1972. Hepatic microsomal ethanol oxidation. Hydrogen peroxide formation and the role of catalase. Eur. J. Biochem. 25: 420–430.
Thurman, R. G., Hesse, S. and Scholz, R. 1974. The role of NADPH-dependent hydrogen peroxide formation and catalase in hepatic microsomal ethanol oxidation, pp. 257–270. In R. G. Thurman, T. Yonetani, J. R. Williamson, and B. Chance (ed.). Alcohol and Aldehyde Metabolizing Systems. Academic Press, New York.
Vatsis, K. P. and Schulman, M. P. 1973a. Peroxidatic ethanol oxidation in homogenates of mouse liver. The Pharmacologist 15: 160.
Vatsis, K. P. and Schulman, M. P. 1973b. Absence of ethanol metabolism in ‘acatalatic’ hepatic microsomes that oxidize drugs. Biochem. Biophys. Res. Commun. 52: 588–594.
Vatsis, K. P. and Schulman, M. P. 1974. ‘Acatalatic’ hepatic microsomes metabolize drugs but not ethanol, pp. 287–298. In R. G. Thurman, T. Yonetani, J. R. Williamson, and B. Chance (ed.). Alcohol and Aldehyde Metabolizing Systems. Academic Press, New York.
Vatsis, K. P., Miller, C. and Schulman, M. P. 1973. Ethanol metabolism in vivo and by hepatic microsomes of mice of different ages. Fed. Proc. 32: 697.
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Vatsis, K.P., Schulman, M.P. (1975). Dissociation of Microsomal Ethanol Oxidation from Cytochrome P-450 Catalyzed Drug Metabolism. In: Cooper, D.Y., Rosenthal, O., Snyder, R., Witmer, C. (eds) Cytochromes P-450 and b5 . Advances in Experimental Medicine and Biology, vol 58. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9026-2_26
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DOI: https://doi.org/10.1007/978-1-4615-9026-2_26
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