Alcohol y metabolismo humano

Carlos Aragón, M. Miquel, M. Correa, C. Sanchis-Segura

Resumen


Uno de los propósitos del presente trabajo es llevar a cabo una revisión actualizada y resumida de los aspectos más relevantes de los procesos de absorción, distribución, biotransformación (metabolismo) y excreción del alcohol. Aunque con variaciones individuales importantes, el alcohol se absorbe mayoritariamente a nivel intestinal, se distribuye por el organismo de forma análoga a la del agua corporal, y se metaboliza en su mayor parte. Dado que la biotransformación fundamental del etanol se produce mediante un metabolismo enzimático oxidativo, hemos reservado un apartado para analizar, en la medida de lo posible, los sistemas enzimáticos responsables de dicha oxidación. Asimismo, con este capítulo hemos querido ofrecer un resumen de los datos disponibles sobre la implicación del acetaldehido, primer metabolito oxidativo del etanol, en los efectos del alcohol. Dicha implicación no se reduce, como tradicionalmente se ha creído, a los efectos tóxicos derivados del consumo de alcohol. Por el contrario, existe un corpus de conocimientos experimentales cada vez más sólido que relaciona al acetaldehido con los efectos euforizantes del alcohol y, en consecuencia, con la capacidad de esta droga de establecer un patrón de consumo repetido. Finalmente, se revisan las interacciones que pueden ocurrir entre el metabolismo del alcohol y la biotransformación de otras sustancias. Dichas interacciones pueden tener lugar siempre que sustancias endógenas o exógenas compartan con el etanol los mismos sistemas enzimáticos. En este sentido, merece especial atención la inducción del P-450 2E1 y otros citocromos P-450 en las células hepáticas provocada por el consumo crónico de alcohol.


Palabras clave


alcohol; acetaldehido; metabolismo; biotransformación

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Referencias


(1) Bogen E. The human toxicology of alcohol. Chapter IV in Alcohol and Man. Emerson, H. (Ed.). The Macmillan company, New York, 1932.

(2) Holford HG. Clinical Pharmacokinetics of ethanol. Clin Pharmacokinetics 1987; 13:273- 92*.

(3) Johnson RD, Horowitz, Maddox AF, Wishart JM, Shearman DJC. Cigarette smoking and rate of gastric emptying: effect on alcohol absortion. British Medical Journal 1991; 302: 20.

(4) Gessner PK. Alcoholes. En Smith CM y Reynard AM (eds). Farmacología. Editorial Panamericana, Montevideo, 1993.

(5) Brown SS, Forrest JAH, Roscoe AP. A controlled trial of fructose in the treatment of acute alcoholic intoxication. Lancet 1972; 2: 898—00.

(6) Jones MK, Jones BM. Ethanol metabolism in women taking oral contraceptives. Alcohol Clin Exp Res 1984; 8: 24—8.

(7) Petersen DR, Erwin VG, Deitrich RA. Brain acetaldehyde metabolism during ethanol consumption. Res. Monographics 1983; 9: 93—9.

(8) Salmela KS, Kaihovaara P, Salaspuro M, Roine RP. Role of catalase in rat gastric mucosal ethanol metabolism in vitro. Alcohol Clin Exp Res

; 20:1011—15.

(9) DeMaster EG, Redfern B, Shirota FN, Nagasawa HT. Differential inhibition of rat tissue catalase by cyanamide. Biochem Pharmacol 1986;

: 2081—85.

(10) Cohen G, Sinet PM, Heikkila R. Ethanol oxidation by rat brain in vivo. Alcohol Clin Exp Res 1980; 4: 366—70.

(11) Goodman DW, Deyking D. Fatty acid ethyl ester formation during ethanol metabolism in vivo. Proc Soc Exp Biol 1963; 113: 65—7.

(12) Mogelson S, Lange LG. Nonoxidative ethanol metabolism in rabbit myocardium purification to homogeneity of fatty acid ethyl ester synthase.

Biochemistry 1984; 23: 4075—81.

(13) Edenberg HJ, Brown CJ. Regulation of human alcohol dehydrogenase genes. Pharmacogenetics 1992; 2: 185—96.

(14) Kitson KE, Weiner H. Ethanol and acetaldehyde metabolism: Past, present and future. Alcohol Clin Exp Res 1996; 20: 82A—2A**.

(15) Lieber CS Ethanol metabolism, cirrhosis and alcoholism. Clin Chim Acta 1997; 257: 59—4**.

(16) Von Wartburg JP, Papenber G J, Aebi H An atypicalhuman alcohol dehydrogenase. Can J J Biochem 1965; 43: 889—98.

(17) Lieber CS, DeCarli LM. Ethanol oxidation by hepatic microsomes: Adaptative increase after ethanol feeding. Science 1968; 162: 917—18.

(18) Lieber CS, DeCarli LM. Hepatic microsomal ethanol-oxidating system. In vitro characteristics and adaptative properties in vivo. J Biol Chem 1970; 245: 2505—12.

(19) Roberts BJ, Shoaf SE, Jeong K-S, Song BJ. Induction of CYP2E1 in liver, kidney, brain and intestine during chronic ethanol administration

and withdrawal: Evidence that CYP 2E1 possesses a rapid phase half-life of 6 hours or less. Biochem Biophis Res Com 1994; 205:1064—71.

(20) Upadhya S, Tirumalai S, Boyd MR, Mori T, Ravindranath V. Cytocrome P4502E (CYP2E1) in brain: Constitutive expression, induction by ethanol and localization by fluorescence in situ hybridation. Arch Biochem Biophys 2000; 373:23-4.

(21) Koop DR Oxidative and reductive metabolism by cytocrome P450 2E1. FASEB J 1992; 6:724—30.

(22) Song BJ, Cederbaum AI. Ethanol inducible cytochrome P450 (CYP2E1): Biochemistry, molecular biology and clinical relevance: 1996

Update. Alcohol Clin Ex Res 1996; 20:138A—46A **.

(23) Hu Y, Ingelman-Sundberg M, Lindros KO. Induction mechanisms of cytochrome P450 2E1 in the liver: Interplay between ethanol treatment

and starvation. Biochem Pharmacol 1995; 50: 155—65.

(24) Takahasi T, Lasker JM, Rosman AS, Lieber CS. Induction of P450 E1 in human liver by ethanol is due to a corresponding increase in encoding

mRNA. Hepatology 1993; 17: 236—45.

(25) Thurman RG, Handler JA. New perspectives in catalase-dependent ethanol metabolism. Drug Metab Rev 1989; 20: 679—88*.

(26) Goth L, Pay A. Genetic heterogeneity in acatalasemia. Electrophoresis 1996; 17: 1302—03.

(27) Berkaloff A, Bourguet J, Favard P, Lacroix J. Biología y fisiología celular: Cloroplastos, peroxisomas, división celular. Ed. Omega. Barcelona,

(28) Yang Q, De Pierre JW. Papid one-step isolation of mouse liver catalase by immobilized metal ion affinity chromatography. Prot Express Purification 1998; 12: 277—83.

(29) Keegan A, Batey R. Dietary carbohydrate accelerates ethanol elimination, but does not alter hepatic alcohol dehydrogenase. Alcohol Clin

Exp Res 1993; 17 :431—3.

(30) Yoshida A, Huang I-Y, Ikawa M. Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals. Proc

Nat Acad Sci USA 1984; 81: 258—61.

(31) Farres J, Takahasi K, Cunningham SJ, Wang X, Wang TT, Weiner H. Effects of changing glutamate 487 to lysine in rat and human liver mitocondrial aldehyde dehydrogenase: A model to study human (Orienal type) class 2 aldehyde dehydrogenase. J Biol Chem 1994; 269:13854—68.

(32) Eriksson CJP. The role of acetaldehyde in the actions of alcohol (update 2000). Alcohol clin Exp Res 2000; 25, 5:15S—32S**.

(33) Raskin NH, Sokoloff L. Enzymes catalyzing ethanol metabolism in neural and somatic tissues of the rat. J Neurochem 1972; 19: 273—82.

(34) Lands WEM. A review of alcohol clearance in humans. Alcohol 1998; 15: 147—60*.

(35) Rout UK. Alcohol dehydrogenases in the brain of mice. Alcoholism Clin Exp Res 1992; 16:286—89.

(36) Gill, K, Menez JF, Lucas D, Deitrich RA. Enzymatic production of acetaldehyde from ethanol in rat brain tissue. Alcohol Clin Exp Res 1992;

: 910—15.

(37) Montoliu C, Valles S, Renau-Piqueras J, Guerri C. Ethanol-induced oxygen radical formation and lipid peroxidation in rat brain: effect of chronic alcohol consumption. J Neurochem 1994;63: 1855—62.

(38) Smith BR, Aragon CMG, Amit Z. Catalase and the production of central acetaldehyde: A possible mediator of the psychopharmacological

effects of ethanol. Addict Biol 1997;2: 277-89*.

(39) Zimatkin SM, Liopo AV, Deitrich RA. Distribution and kineticks of ethanol metabolism in rat brain. Alcohol Clin Exp Res 1998; 22: 1623—27.

(40) Aragon CMG, Stotland LM, Amit Z. Studies on ethanol-brain catalase interaction: Evidence for central ethanol oxidation. Alcohol Clin Exp

; Res. 15: 165—69.

(41) Moreno S, Mugnaini E, Ceru MP. Immunocytochemical localization of catalase in the central nervous system of rat. J Histochem Cytochem

; 43: 1253—67.

(42) Aragon CMG, Rogan F, Amit Z. Ethanol metabolism in rat brain homogenates by a catalase-H202 system. Biochem. Pharmacol 1992; 44:

—98.

(43) Zimatkin SM, Deitrich RA. Aldehyde dehydrogenase activities in the brains of rats and mice genetically selected for different sensivity to

alcohol. Alcohol Clin Exp Res; 1995; 19: 1300—06.

(44) Levitt MD, Levitt DG. The critical rol of the rate of ethanol absorption in the interpretation of the studies purporting to demostrate gastric

metabolism of ethanol. J Pharmacol Ex Ther 1994; 269: 297—04.

(45) Laposata EA, Lang LG. Presence of non-oxidative ethanol metabolism in humans organs commonly damaged by ethanol abuse. Science

; 231: 497—99.

(46) Wrighton SA, Pai JK, Mueller GC. Demonstration of two unique metabolites of arachidonic acid from phobol ester-stimulated bovine

lymphocites. Carcinogenesis 1983; 4: 1247—51.

(47) Omodeo-Sale F, Lindi CL, Palestini P, Maserini M. Role of phosphatidylethanol in membrans. Effects of membrane fluidity tolerance to ethanol and activity of membran bound enzimes. Biochemistry 1991; 30: 2477—82.

(48) Chao HM.. Alcohol and the mystique of flushing. Alcohol Clin Exp Res 1995; 19: 104—09**.

(49) Kupari M, Lindros K, Hillbom M, Heikkilä J, Ylikahri R. Cardiovascular effects of acetaldehyde accumaltion after ethanol ingestion: Their modification by beta-adrenergic blockade and alcohol dehydrogenase inhibition. Alcohol Clin Exp Res 1983;7:283—88.

(50) Inoue K, Fukunaga M, Yamasawa K Accumulation of acetaldehyde in alcohol-sensitive Japanese: Relation to ethanol and acetaldehyde oxi-dizing capacity. Alcohol Clin Exp Res 1984;8:319—22.

(51) Lindros KO. Acetaldehyde: its metabolism and role in the actions of alcohol. En: Research advances in alcohol and drug problems. 1978;

-76. Israel, Y. et al., (eds). Plenum. NY.

(52) Aragon CMG, Abitbol M, Amit Z. Acetaldehyde may mediate reinforcement and aversion produced by ethanol. An examination using conditioned taste aversion paradigm. Neuropharmacology 1986; 25: 79—3.

(53) Bergamaschi S, Yoyovoni S, Rius RA, Trabucchi M. Acute ethanol and acetaldehyde administration produce similar effects on L-type calcium

channels in rat brain. Alcohol 1988; 5: 337—40.

(54) Zimatkin SM, Deitrich RA. Ethanol metabolism in the brain. Adicction Biol 1997;2:387—399*.

(55) Kuriyama S, Okuma S, Tomono S, Hirouchi M. Effects of alcohol and acetaldehyde on metabolism and function of neurotransmitter systems in cerebral cortical neurons in primary culture. Alcohol Alcohol 1987; spl.1: 685—89.

(56) Poldrugo F, Snead OC. Effect of ethanol and acetaldehyde on gamma-hydroxybutyric acid in rat brain and liver. Subs. Alcohol Actions/Misuse

; 5:263—271.

(57) Barbaccia ML, Bosio A, Spano PF, Trabucchi M. Ethanol metabolism and striatal dopamine turnover. J. Neural Transmiss 1982; 53: 169—77.

(58) Pastoric M, Boyadjieva N, Sarkar DK. Comparison of the effects of alcohol and acetaldehyde on proopiomelanocortin mRNA levels and β-

endorphin secretion from hypothalamic neurons in primary cultures. Mol. Cel. Neurosci 1994; 5: 580—586.

(59) Reddy BV, Sarkar DK. Effect of alcohol, acetaldehyde and salsolinol on β-endorphin secretion from the hypotalamic neurons in primary cultures. Alcohol Clin Exp Res 1993;17: 161-1267.

(60) Reddy BV, Boyadjeva N, Sarkar DK. Effect of ethanol, propanol, butanol and catalase enzyme blockers on β−endorphin secretion from

primary cultures of hypotalamic neurons: Evidence for a mediatory role of acetaldehyde in ethanol stimulation of β-endorphin release.

Alcohol Clin Exp Res 1995;19: 339—344.

(61) Walsh MJ. Role of acetaldehyde in the interactions of ethanol with neuroamines, 233-266. En: Biochemical aspects of alcohol; Roach, M.K. et al. (eds). 1971 University of Texas Press.

(62) Thadani PV, Truitt EB. Effect of acute ethanol or acetaldehyde administration on the uptake, release, metabolism and turnover rate of norepinephrine in rat brain. Biochem Pharmacol 1977;26: 1147-1150.

(63) Ortiz A, Griffiths PJ, Littleton JM. A comparison of the effects of chronic administration of ethanol and acetaldehyde to mice: Evidence

for a role of acetaldehyde in ethanol dependence. J Pharmacy Pharmacol 1974; 6: 349—60.

(64) Truitt EB Walsh MJ. The role of acetaldehyde in the actions of ethanol. En: The biology of alcoholism, vol.1. 161-195. Kissin, B.; Begleiter, H.

(eds.) 1971 New York: Plenum Press.

(65) Zimatkin SM. Histochemical study of aldehyde dehydrogenase in the rat CNS. J Neurochem 1991;56: 1—11.

(66) Mizoi Y, Ijiri I, Tatsuno Y, Kijima T, Fujiwara S, Adachi J, Hishida S. Relationship between facial flushing and acetaldehyde levels after

alcohol intake. Pharmacol Biochem Behav 1979;10:300—11.

(67) Gianoulakis C, Dewaele JP, Thavundayil J. Implication of the endogenous opioid system in excesive ethanol consumption. Alcohol

;13: 19—3.

(68) Terenius L. Alcohol addiction (alcoholism) and the opioid system 1. Alcohol 1996;13: 31-34.

(69) Takayama S, Uyeno ET. Intravenous self administration of ethanol and acetaldehyde by rats. Japanese J Psychopharmacol 1985;5: 329—

(70) MyersWD, Ng K, Singer G. Effects of naloxone and buprenorphine on intravenous acetaldehyde self-injection in rats. Phisiol Behav 1984a;33: 807—11.

(71) MyersWD, Ng K, Singer G. Ethanol preference in rats with a prior history of acetaldehyde selfadministration. Experientia 1984b;40: 1008—

(72) Brown ZW, Amit Z, Smith BR. Intraventricular self-administration of acetaldehyde but not ethanol, in naive laboratory rats.Psychopharmacology

; 64: 271—76.

(73) Rodd-Henricks ZA, Zaffaroni A, Goldstein A, McBride WJ, Li TK. Alcohol Preferring (P) rats self-administer acetaldehyde directly into the

posterior VTA (abstract). Alcohol Clin Exp Res 2000;(Suppl 5) 24:52 A.

(74) Myers RD, Veale WL. Alterations in volitional alcohol intake produced in rats by chronic intra- ventricular infusions of acetaldehyde, paraldehyde

or methanol. Arch. Int. Pharmacodyn 1969;180: 100—13.

(75) Smith BR, Amit Z, Splawinsky J. Conditioned place preference induced by intraventricular infusions of acetaldehyde. Alcohol 1984;1:193—195.

(76) Smith BR, Aragon CMG, Amit Z. A time-dependent biphasic effect of an acute ethanol injection on 3-methoxy 4-hydroxyphenylethylene glycol sulfate in rat brain. Biochem Pharmacol 1985; 34: 1311—14.

(77) Quetermont E, De Witte P. Conditioned stimulus preference after acetaldehyde but not ethanol injections. Pharmacol biochem Behav

;68:449—454.

(78) Yamauchi M, Maezawa Y, Mizuhara Y, Ohata M, Hirakawa J, Nakajima H, Toda G. Polymorphisms in alcohol metabolizing enzyme genes

and alcoholic cirrhosis in Japanese patients. Hepatology 1995; 22: 1136—42.

(79) Higuchi S. Polymorphisms of ethanol metabolizing enzyme genes and alcoholism. Alcohol Alcohol 1994;29:29—34.

(80) Peachey JE, Brien JF, Loomis CW, Rogers BJ. A study of the calcium carbimide-ethanol interaction in man: Symptom responses. Alcohol Clin Exp Res 1980;4:32—329.

(81) Schuckit MA, Duby J. Alcohol-related flushing and the risk for alcoholism in sons of alcoholics. J Clin Psychiatry 1982;43:415—418.

(82) Hunt WA. Role of acetaldehyde in the actions of ethanol on the brain-A review. Alcohol 1996 13: 147—51*.

(83) Tabakoff B, Anderson RA, Ritzmann, RF. Brain acetaldehyde after ethanol administration. Biochem Pharmacol 1976;25: 1305—1309.

(84) Deitrich RA. The especifity of ethanol. En: Advances on biomedical alcohol research. 1987;131-38. Lindros KO (ed). Pergamon Press,

New York, 1987.

(85) Amit Z, Smith BR. A Multi-dimensional examination of the positive reinforcing properties of acetaldehyde. Alcohol 1985; 2: 367—70.

(86) Amit Z, Aragon CMG, Smith BR. Alcohol metabolizing enzymes as possible markers mediating voluntary consumption. Canadian J. Public

Health 1986; 77 sup. 1: 15—20.

(87) Amit Z, Smith BR. The role of acetaldehyde in alcohol addiction. Human metabolism of alcohol. 1989; Vol II; 194-198 Cro, KE, Batt RD.

(eds.) CRC Press Inc.

(88) Myers WD, Ng K, Singer G. Intravenous selfadministration of acetaldehyde in the rat as a functions of schedule, food deprivation and

photoperiod. Pharmacol Biochem Behav 1982;17: 807—11.

(89) Kenney WC. Interaction of acetaldehyde with phospholipids. Gastroenterology 1980; 79:1030—32.

(90) Shiohara E, Tsukada M, Chiba S, Yamazaki H, Nishiguchi K, Miyamoto R, Nakanishi S. Effect if chronic administration of acetaldehyde by

inhalation (Na+K+)-activated adenosine triphosphatase activity of rat brain membranes. Toxicology 1986;34: 277—284.

(91) Lumeng L, Lin, RC. Protein acetaldehyde aducts as biochemical markers of alcohol consumption. En: Measuring alcohol consumption.

; 161-82; Litten, R. (ed). The Humana press Inc.

(92) Jennet RB, Sorrell MF, Saffari-Fard A, Ockner JL Tuma DJ. Preferential covalent binding of acetaldehyde to the α-chain of purified rat liver tubulin. Hepatology 1989; 9: 57—2.

(93) Nuñez-Vergara LJ, Yudelevich J, Squella JA Speisky H. Drug-acetaldehyde interactions during ethanol metabolism in vitro. Alcohol

Alcohol 1991; 26:139—46.

(94) Deitrich RA, Erwin VG. Interaction of amine metabolism and alcohol actions. En: Monoamine oxidase and disease, 275-89. Academic Press, New York, 1984.

(95) Rommelspacher H, Buchau C, Weiss J. Harman induces preference for ethanol in rats: Is the effect specific for ethanol?. Pharmacol Biochem

Behav 1987;26: 749—755.

(96) Brown ZW, Amit Z, Smith BR. Intraventricular self-administration of acetaldehyde and voluntary consumption of ethanol in rats. Behav. Neural Biol 1980; 28: 150—55.

(97) Smolen TN, Collins AC. Behavioral effects of ethanol and salsolinol in mice selectively bred for acute sensivity to ethanol. Pharmacol Biochem

Behav 1984;20:281—28.

(98) Lieber CS. Mechanisms of ethanol-drug-nutrition interactions. J Toxicol Clin Toxicol 1994;32:631—81.

(99) Nordmann R. Alcohol and antioxidant systems. Alcohol 1994; 29:513—22.

(100) Lieber CS. Cytochrome P-250 2E1: Its Physiological and pathological role. Physiol Rev 1997; 77:517—44*.

(101) Goldberg DM, Parkes JG, Hahn S. Microsomal induction, alcohol, and lipoprotein metabolism: Is there a three-way relationship?. Clin Biochem 1989; 22:57—7*.

(102) Hoensch H. Ethanol asenzyme inducer and inhibitor. Pharmac Ther 1987; 33;12—8.

(103) Koop DR, Coon MJ. Ethanol oxidation and toxicity: Role of alcohol P-450 oxygenase. Alcohol Clin Exp Res 1986; 10:44S—8S.

(104) Djordjevic D, Nikolic J, Stefanovic V. Ethanol interactions with other cytochrome P450 substrates, drugs, xenobiotics, and carcinogens. Pathol Biol 1998; 46:760—70*.

(105) McClain CJ, Kromhout JP, Peterson FJ Holtzman JL. Potentiation of aetaminophen hepatotoxicity by alcohol. JAMA 1980; 244:251—3.

(106) Banda PW, Quart BD. The effect of alcohol consumption on the metabolism of acetaminophen in man. Res Commun Pathol Pharmacol

; 38:57—0.

(107) Duester G. Alcohol dehydrogenase as a critical mediator of retinoic acid synthesis from vitamin A in the mouse embryo. J Nutr 1998; 128:459S—62S.

(108) Leo MA, Lieber CS. Alcohol, vitamin A, and bcarotene: Adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr

; 69:1071—85*.




DOI: https://doi.org/10.20882/adicciones.541

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