Acceleration of Ethanol Metabolism by High Ethanol Concentrations and Chronic Ethanol Consumption: Role of the Microsomal Ethanol Oxidizing System (MEOS)

  • Shohei Matsuzaki
  • R. Teschke
  • K. Ohnishi
  • C. S. Lieber


Chronic ethanol consumption has been shown to be associated with an acceleration of ethanol metabolism in man (1–3) and rats (4–6). This phenomenon could not be explained by the activity of alcohol dehydrogenase itself, as reviewed elsewhere (7). Some other possible mechanisms have been suggested, including the adaptive increase of the microsomal ethanol oxidizing system (MEOS) (5, 8, 9), increased mitochondrial reoxidation of NADH (10–12) and enhanced catalase-H2O2 mediated peroxidation (13, 14).


Chronic Ethanol Liver Slice Ethanol Oxidation Ethanol Metabolism Chronic Ethanol Consumption 
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  1. 1.
    MISRA PS, LEFEVERE A, ISHII H, RUBIN E, LIEBER CS: Increase in ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats. Am J Med 51s 346–351, 1971CrossRefGoogle Scholar
  2. 2.
    KATER RM, CARULLI N, IBER FL: Differences in the rate of ethanol metabolism in recently drinking alcoholic and nondrinking subjects. Am J Clin Nutr 22: 1608–1617, 1969PubMedGoogle Scholar
  3. 3.
    MEZEY E, TOBON F: Rates of ethanol clearance and activities of the ethanol-oxidizing enzymes in chronic alcoholic patients. Gastroenterology 61: 707–715, 1971PubMedGoogle Scholar
  4. 4.
    HAWKINS RD, KALANT H, KHANNA JM: Effect of chronic intake of ethanol on rate of ethanol metabolism. Canad J Physiol Pharmacol 44: 241–257, 1966CrossRefGoogle Scholar
  5. 5.
    LIEBER CS, DE CARLI LM: The role of the microsomal ethanol oxidizing system (MEOS) for ethanol metabolism in vivo. J Pharmacol Exp Ther 181: 279–287, 1972PubMedGoogle Scholar
  6. 6.
    VIDELA L, BERNSTEIN J, ISRAEL Y: Metabolic alterations produced in the liver by chronic ethanol administration. Increased oxidative capacity. Biochem J 134: 507–514, 1973PubMedGoogle Scholar
  7. 7.
    LIEBER CS: Hepatic and metabolic effects of alcohol (1966–1973). Gastroenterology 65: 821–846, 1973PubMedGoogle Scholar
  8. 8.
    LIEBER CS, DE CARLI LM: Ethanol oxidation by hepatic microsomes: Adaptive increase after ethanol feeding. Science 162: 917–918, 1968PubMedCrossRefGoogle Scholar
  9. 9.
    LIEBER CS, DECARLI LM: Hepatic microsomal ethanol oxidizing system: In vitro characteristics and adaptive properties in vivo. J Biol Chem 245: 2505–2512, 1970PubMedGoogle Scholar
  10. 10.
    VIDELA L, ISRAEL Y: Factors that modify the metabolism of ethanol in rat liver and adaptive changes produced by its chronic administration. Biochem J 118: 275–281, 1970PubMedGoogle Scholar
  11. 11.
    BERNSTEIN J, VIDELA L, ISRAEL Y: Metabolic alterations produced in the liver by chronic ethanol administration. II. Changes related to energetic parameters of the cell. Biochem J 134: 515–521, 1973PubMedGoogle Scholar
  12. 12.
    ISRAEL Y, VIDELA L, VIDELA VF, BERNSTEIN J: Effects of chronic ethanol treatment and thyroxine administration on ethanol metabolism and liver oxidative capacity. J Pharmacol Exp Ther 192: 565–574, 1975PubMedGoogle Scholar
  13. 13.
    THURMAN RG, LEY HG, SCHOLZ R: Hepatic microsomal ethanol oxidation. Hydrogen peroxide formation and the role of catalase. Eur J Biochem 25: 420–430, 1972PubMedCrossRefGoogle Scholar
  14. 14.
    THURMAN RG: Induction of hepatic microsomal reduced nicotinamide adenine dinucleotide phosphate-dependent production of hydrogen peroxide by chronic prior treatment with ethanol. Molec Pharmacol 9: 670–675, 1973Google Scholar
  15. 15.
    KORSTEN MA, MATSUZAKI S, FEINMAN L, LIEBER CS: High blood acetaldehyde levels after ethanol administration in alcoholics. New Eng J Med 292: 386–389, 1975PubMedCrossRefGoogle Scholar
  16. 16.
    ARSLANIAN MJ, PASCOE E, REINHOLD JG: Rat liver alcohol dehydrogenase. Purification and properties. Biochem J 125: 1039–1047, 1971PubMedGoogle Scholar
  17. 17.
    OKUDA K, TAKIGAWA N: Rat liver 5 β-cholestane-3α,7α,12α, 26-tetrol dehydrogenase as a liver alcohol dehydrogenase. Biochim BiophysActa 220: 141–148, 1970PubMedGoogle Scholar
  18. 18.
    MISTILIS SP, GARSKE A: Induction of alcohol dehydrogenase in liver and gastrointestinal tract. Aust Ann Med 18: 227–231, 1969PubMedGoogle Scholar
  19. 19.
    LUNDQUIST F, WOLTHERS H: The kinetics of alcohol elimination in man. Acta Pharmacol 14: 265–289, 1958CrossRefGoogle Scholar
  20. 20.
    MAKAR AB, MANNERING GJ: Pyrazole inhibition and kinetics of ethanol metabolism in the intact rat and monkey. Biochem Pharmacol 19: 2017–2022, 1970PubMedCrossRefGoogle Scholar
  21. 21.
    REYNIER M: Pyrazole inhibition and kinetic studies of ethanol and retinol oxidation catalyzed by rat liver alcohol dehydrogenase. Acta Chem Scand 23: 1119–1129, 1969PubMedCrossRefGoogle Scholar
  22. 22.
    LINDROS KO, OSHINO N, PARRILLA R, WILLIAMSON J: Characteristics of ethanol oxidation on flavin and pyridine nucleotide fluorescence changes in perfused rat liver. J Biol Chem 249: 7956–7963, 1974PubMedGoogle Scholar
  23. 23.
    MEZEY E, TOBON F: Rates of ethanol clearance and activities of the ethanol-oxidizing enzymes in chronic alcoholic patients. Gastroenterology 61: 707–715, 1971PubMedGoogle Scholar
  24. 24.
    ISERI OA, LIEBER CS, GOTTLIEB LS: The ultrastructure of fatty liver induced by prolonged ethanol ingestion. Am J Pathol 48: 535–555, 1966PubMedGoogle Scholar
  25. 25.
    RUBIN E, HUTTERER F, LIEBER CS: Ethanol increases hepatic smooth endoplasmic reticulum and drug-metabolizing enzymes. Science 159: 1469–1470, 1968PubMedCrossRefGoogle Scholar
  26. 26.
    LANE BP, LIEBER CS: Ultrastructural alterations in human hepatocytes following ingestion of ethanol with adequate diets. Am J Pathol 49: 593–603, 1966PubMedGoogle Scholar
  27. 27.
    RUBIN E, LIEBER CS: Early fine structural changes in the human liver induced by alcohol. Gastroenterology 52: 1–13, 1967PubMedGoogle Scholar
  28. 28.
    RUBIN E, LIEBER CS: Alcohol-induced hepatic injury in non-alcoholic volunteers. N Eng J Med 278: 869–876, 1968CrossRefGoogle Scholar
  29. 29.
    ISHII H, JOLY J-G, LIEBER CS: Effect of ethanol on the amount and enzyme activities of hepatic rough and smooth microsomal membranes. Biochem Biophys Acta 291: 411–420, 1973PubMedCrossRefGoogle Scholar
  30. 30.
    ORME-JOHNSON WH, ZIEGLER DM: Alcohol mixed function oxidase activity of mammalian liver microsomes. Biochem Biophys Res Commun 21: 78–82, 1965PubMedCrossRefGoogle Scholar
  31. 31.
    ZIEGLER DM: Discussion in Microsomes and Drug Oxidation. RW Estabrook, JR Gillette and KC Liebman (eds.). Baltimore, Williams and Wilkins, 1972, pp. 458Google Scholar
  32. 32.
    TESCHKE R, HASUMURA Y, LIEBER CS: Hepatic microsomal alcohol oxidizing system. Affinity for methanol, ethanol and propanol. J Biol Chem 250: 7397–7404, 1975PubMedGoogle Scholar
  33. 33.
    CHANCE B, OSHINO N: Kinetics and mechanisms of catalase in peroxisomes of the mitochondrial fraction. Biochem J 122: 225- 233, 1971PubMedGoogle Scholar
  34. 34.
    REDMAN CM, GRAB DJ, IRUKULLA R: The intracellular pathway of newly formed rat liver catalase. Arch Biochem Biophys 152: 496–501, 1972PubMedCrossRefGoogle Scholar
  35. 35.
    KEILIN D, HARTREE EF: Properties of catalase. Catalysis of compiled oxidation of alcohols. Biochem J 39: 293–301, 1945Google Scholar
  36. 36.
    BOVERIS A, OSHINO N, CHANCE B: The cellular production of hydrogen peroxide. Biochem J 128: 617–630, 1972PubMedGoogle Scholar
  37. 37.
    OSHINO N, CHANCE B, SIES H, BUCHER T: The role of H202 generation in perfused rat liver and the reaction of catalase compound I and hydrogen donors. Arch Biochem Biophys 154: 117- 131,1973PubMedCrossRefGoogle Scholar
  38. 38.
    OSHINO N, JAMIESON D, CHANCE B: The properties of hydrogen peroxide production under hyperoxic and hypoxic conditions of perfused rat liver. Biochem J 146: 53–65, 1975PubMedGoogle Scholar
  39. 39.
    LESTER B, BENSON GD: Alcohol oxidation in rats inhibited by pyrazole oximes and amides. Science 169: 282–284, 1970PubMedCrossRefGoogle Scholar
  40. 40.
    PAPENBERG J, von WARTBURG JP, AEBI H: Metabolism of ethanol and fructose in the perfused rat liver. Enzym Biol Clin 11: 237–250, 1970Google Scholar
  41. 41.
    FEYTMANS E, LEIGHTON F: Effects of pyrazole and 3-amino-l, 2, 4-triazole on methanol and ethanol metabolism by the rat. Biochem Pharmacol 22: 349–360, 1973PubMedCrossRefGoogle Scholar
  42. 42.
    ISSELBACHER KJ, CARTER EA: Ethanol oxidation by liver microsomes: Evidence against a separate and distinct enzyme system. Biochem Biophys Res Commun 39: 530–537, 1970PubMedCrossRefGoogle Scholar
  43. 43.
    ROACH MK, REESE WN, CREAVEN PJ: Ethanol oxidation in the microsomal fraction of rat liver. Biochem Biophys Res Commun 36: 596–602, 1969PubMedCrossRefGoogle Scholar
  44. 44.
    TESCHKE R, HASUMURA Y, LIEBER CS: Hepatic microsomal ethanol oxidizing system: Solubilization, isolation and characterization. Arch Biochem Biophys 163: 404–415, 1974PubMedCrossRefGoogle Scholar
  45. 45.
    OHNISHI K, LIEBER CS: Reconstitution of the hepatic microsomal ethanol oxidizing system. Fed Proc 35: 706, 1976Google Scholar
  46. 46.
    COMAI K, GAYLOR JL: Existence and separation of three forms of cytochrome P-450 from rat liver microsomes. J Biol Chem 248: 4949–4955, 1973Google Scholar
  47. 47.
    LEVIN W, RYAN D, WEST S, LU AY: Preparation of partially purified lipid-depleted cytochrome P-450 and reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase from rat liver microsomes. J Biol Chem 249: 1747–1754, 1974PubMedGoogle Scholar
  48. 48.
    KALANT H, KHANNA JM, ENDRENYI I: Effect of pyrazole on ethanol metabolism in ethanol treated rats. Canad J Physiol Pharmacol 53: 416–422, 1975CrossRefGoogle Scholar
  49. 49.
    STEIN WS, LIEBER CS, LEEVY CM, CHERRICK GR, ABELMANN WH: The effect of ethanol upon systemic and hepatic blood flow in man. Am J Clin Nutr 13: 68–74, 1963PubMedGoogle Scholar
  50. 50.
    BERRY MN, FRIEND DS: High yield preparation of isolated rat liver parenchymal cells. A biochemical and fine structural study. J Cell Biol 43: 506–520, 1969PubMedCrossRefGoogle Scholar
  51. 51.
    JEEJEEBHOY KN, HO J, GREENBERG R, PHILLIPS MJ, BRUCE-ROBERTSON A, SODTKE U: Albumin fibrinogen and transferrin synthesis in isolated rat hepatocyte suspension. Biochem J 146; 141–155, 1975PubMedGoogle Scholar
  52. 52.
    BONNICHSEN R, BRINK NG: Liver alcohol dehydrogenase. In Methods of Enzymology, vol 1. SP Colowick and NO Kaplan (eds.). New York, Academic Press, 1965. pp. 495–503CrossRefGoogle Scholar
  53. 53.
    LUCK H: Catalase. In Methods of Enzymatic Analysis. HU Bergmeyer, (ed.). New York, Academic Press, 1963. pp. 885–894Google Scholar
  54. 54.
    GRUNNET N, QUISTORFF B, THIEDEN His Rate limiting factors in ethanol oxidation by isolated rat liver parenchymal cells. Eur J Biochem 40: 275–282, 1973PubMedCrossRefGoogle Scholar
  55. 55.
    TESCHKE R, HASUMURA Y, LIEBER CS: Hepatic ethanol metabolisms Respective roles of alcohol dehydrogenase, the microsomal ethanol oxidizing system and catalase. Arch Biochem Biophys 175: 635–643, 1976PubMedCrossRefGoogle Scholar
  56. 56.
    THIEDEN HI: The effect of ethanol concentration on ethanol oxidation rate in rat liver slices. Acta Chem Scand 25: 3421–3427, 1971PubMedCrossRefGoogle Scholar
  57. 57.
    DE CARLI LM, LIEBER CS: Fatty liver in the rat after prolonged intake of ethanol with a nutritionally adequate liquid diet. J Nutr 91: 331–336, 1967Google Scholar
  58. 58.
    MATSUZAKI S, LIEBER CS: ADH independent ethanol oxidation in the liver and its increase by chronic ethanol consumption. Gastroenterology 69: A45/845, 1975Google Scholar
  59. 59.
    SVOBODA DJ, MANNING RTs Chronic alcoholism with fatty metamorphosis of the liver. Mitochondrial alterations in hepatic cells. Am J Pathol 44: 645–662, 1964PubMedGoogle Scholar
  60. 60.
    KIESSLING K-H, PILSTROM L: Ethanol and the human liver. Structural and metabolic changes in liver mitochondria. Cyto- biologie 4s 339–348, 1971Google Scholar
  61. 61.
    FRENCH SW: Fragility of liver mitochondria in ethanol-fed rats. Gastroenterology 54: 1106–1114, 1968PubMedGoogle Scholar
  62. 62.
    CEDERBAUM AI, LIEBER CS, RUBIN Es Effect of chronic ethanol treatment on mitochondrial functions damage to coupling site I. Arch Biochem Biophys 165: 560–569, 1974PubMedCrossRefGoogle Scholar
  63. 63.
    CEDERBAUM AI, LIEBER CS, TOTH A, BEATTIE DS, RUBIN E: Effects of ethanol and fat on the transport of reducing equivalents into rat liver mitochondria. J Biol Chem 248: 4977–4986, 1973PubMedGoogle Scholar
  64. 64.
    ERIKSSON CJ: Ethanol and acetaldehyde metabolism in rat strains genetically selected for their ethanol preference. Biochem Pharmacol 22: 2283–2292, 1973PubMedCrossRefGoogle Scholar
  65. 65.
    TOTTMAR O, MARCHNER H: Characteristics of the acetaldehyde oxidation in rat liver, and the effects of antabuse, 4-methyl- pyrazole and unknown dietary factors on the hepatic output of acetaldehyde. In The Role of Acetaldehyde in the Actions of Ethanol, vol 23. KO Lindros and CJP Ericksson, (eds.). The Finnish Foundation for Alcohol Studies, Helsinki, 1975. pp. 47–66Google Scholar
  66. 66.
    HASUMURA Y, TESCHKE R, LIEBER CS: Acetaldehyde oxidation by hepatic mitochondria. Decrease after chronic ethanol consumption. Science 189: 727–729, 1975PubMedCrossRefGoogle Scholar
  67. 67.
    HASUMURA Y, TESCHKE R, LIEBER CS: Characteristics of acetaldehyde oxidation in rat liver mitochondria. J Biol Chem, in press, 1976Google Scholar
  68. 68.
    GORDON E: ATP metabolism in an ethanol-induced fatty liver. Alcoholism: Clinical and Experimental Research, in press, 1977Google Scholar
  69. 69.
    VEECH RL, EGGLESTON LV, KREBS HA: The redox state of free nicotinamide-adenine dinucleotide phosphate in the cytoplasm of rat liver. Biochem J 115: 609–619, 1969PubMedGoogle Scholar
  70. 70.
    GRUNDIN R: Metabolic interaction of ethanol and alprenolol in isolated liver cells. Acta Pharmacol Toxicol 37: 185–200, 1975CrossRefGoogle Scholar
  71. 71.
    DALZIEL K, DICKINSON FM: The activity of liver alcohol dehydrogenase with nicotinamide-adenine dinucleotide phosphate as coenzyme. Biochem J 95: 311–320, 1965PubMedGoogle Scholar
  72. 72.
    BLOMSTRAND R, THEORELL H: Inhibitory effect on ethanol oxidation in man after administration of 4-methylpyrazole. Life Sci 9: 631–640, 1970CrossRefGoogle Scholar
  73. 73.
    SALASPURO MP, LINDROS KO, PIKKARAINEN P: Ethanol and galactose metabolism as influenced by 4-methylpyrazole in alcoholics with and without nutritional deficiency. Ann Clin Res 7: 269–272, 1975PubMedGoogle Scholar
  74. 74.
    THEORELL H, YONETANI T: On the effects of some heterocyclic compounds on the enzymic activity of liver alcohol dehydrogenase. Acta Chem Scand 5: 1105–1126, 1951CrossRefGoogle Scholar
  75. 75.
    RYDBERG U, BUIJTEN J, NERI A: Kinetics of some pyrazole derivatives in the rat. J Pharm Pharmacol 24: 651–652, 1972PubMedCrossRefGoogle Scholar
  76. 76.
    DEITRICH RA, COLLINS AC, ERWIN VG: Effect of pyrazole in vivo on aldehyde metabolism in rat liver and brain. Biochem Pharmacol 20: 2663–2669, 1971PubMedCrossRefGoogle Scholar
  77. 77.
    DOMSCHKE S, DOMSCHKE W, LIEBER CS: Hepatic redox state: Attenuation of the acute effects of ethanol induced by chronic ethanol consumption. Life Sci 15: 1327–1334, 1974PubMedCrossRefGoogle Scholar
  78. 78.
    NEWMAN HW, LEBMAN AJ, CUTTING WC: Effect of dosage on rate of disappearance of alcohol from its blood stream. J Pharmacol 61: 58–61, 1937Google Scholar
  79. 79.
    GUYNN RW, PIEKLIK JR: Dependence on dose of the acute effects of ethanol on liver metabolism in vivo. J Clin Invest 56: 1411–1419, 1975PubMedCrossRefGoogle Scholar
  80. 80.
    THEORELL H, NYGAARD AP, BONNICHSEN R: Studies on liver alcohol dehydrogenase. III. The influence of pH and some anions on the reaction velocity constants. Acta Chem Scand 9: 1148- 1165, 1955CrossRefGoogle Scholar
  81. 81.
    von WARTBURG J-P, BETHUNE JL, VALLEE BL: Human liver alcohol dehydrogenase. Kinetic and physiochemical properties. Biochem 3: 1775–1782, 1964CrossRefGoogle Scholar
  82. 82.
    GERSHMAN H: Acetaldehyde-ethanol change in vivo during ethanol oxidation. Arch Biochem Biophys 168: 327–330, 1975PubMedCrossRefGoogle Scholar
  83. 83.
    THURMAN RG, BRENTZEL HJ: The role of alcohol dehydrogenase in microsomal ethanol oxidation and the adaptive increase in ethanol metabolism due to chronic treatment with ethanol. Alcoholism: Clinical and Experimental Research 1: in press, 1977.Google Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Shohei Matsuzaki
    • 1
    • 2
  • R. Teschke
    • 1
    • 2
  • K. Ohnishi
    • 1
    • 2
  • C. S. Lieber
    • 1
    • 2
  1. 1.Laboratory of Liver Disease, Nutrition and AlcoholismVeterans Administration HospitalBronxUSA
  2. 2.Mount Sinai School of MedicineCity University of New York (CUNY)USA

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