The Metabolism of Alcohol in Normals and Alcoholics: Enzymes

Wartburg, J. P. von

doi:10.1007/978-1-4615-6525-3_2

Cited by 43 publications

(9 citation statements)

References 118 publications

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“…The results are entirely consistent with the three locus hypothesis and they are also consistent with the previous studies on human liver ADH. The experiments with different alcohols as substrate agree with the previous reports (von Wartburg et al 1964Wartburg et al , 1965Wartburg et al , 1966Wartburg et al , 1968Blair & Vallee, 1966;von Wartburg, 1971) that human S D H has a wide and varied substmte specificity, but they also revealed marked differences in specificity among the ADH,, ADH, and ADH, isozymes. The ADH, isozymes for example were found to be most active with ethanol, ally1 alcohol, sec-propanol and cyclohexanol ; ADH, isozymes characteristic of the 'usual' pH ratio phenotype were most active with ethanol, butanol, octanol and sec-butanol ; whereas the ADH, isozymes showed relatively very high activities with the longer chained alcohols, butanol, amyl alcohol, heptanol and octanol.…”

Section: Discussionsupporting

confidence: 90%

“…Previous work using crude tissue homogenates and also purified preparations indicated that human liver ADH has a broad substrate specificity and is capable of catalysing the oxidation of a wide range of alcohols in the presence of NAD and the reduction of many corresponding aldehydes in the presence of NADH (von Wartburg, Bethune & Vallee, 1964;von Wartburg, Papenberg & Aebi, 1965;von Wartburg & Papenberg, 1966;von Wartburg, 1971). Several pharmacologically actiTe alcohols such as Ronicol (P-pyridyl carbinol) and Myanesin (toloxy-1,2-propanediol) and aldehydes such as chloral hydrate and Acetaldol (P-hydroxybutyraldehyde) have also been shown to act as substrates for human liver ADH (von Wartburg & Schurch, 1968).…”

Section: Introductionmentioning

confidence: 99%

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Studies on the properties of the human alcohol dehydrogenase isozymes determined by the different loci ADH₁, ADH₂, ADH₃

Smith

Hopkinson

Harris

1973

Annals of Human Genetics

113

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Studies on the properties of the human alcohol dehydrogenase isozymes determined by the different loci ADH₁, ADH₂, ADH₃

Smith

Hopkinson

Harris

1973

Annals of Human Genetics

113

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“…Of particular interest, however, are reports of liver (4) and pancreatic injury (5) following exposure of experimental animals to allyl alcohols, a compound which was produced by fecal specimens of 30% of our normal individuals. It seems possible that the toxicity of the higher alcohols might be enhanced in alcoholic patients since these alcohols and ethanol compete for metabolism by the same alcohol and aldehyde dehydrogenase systems (6,7). At low blood alcohol concentrations, hepatic clearance of an alcohol is highly efficient, and only a small percentage of the alcohol in the portal blood passes out of the liver.…”

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confidence: 96%

Hypothesis: Metabolic Activity of the Colonic Bacteria Influences Organ Injury From Ethanol

1982

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Incubation of human fecal homogenates with ethanol (0.078 g m per dl) resulted in accumulation of increased quantities of higher alcohols and other unidentified metabolites when compared with homogenates incubated without ethanol. Studies in rats demonstrated nearly perfect equilibration between blood and colonic luminal ethanol suggesting that the colonic flora in alcoholics is chronically exposed to ethanol concentrations in the range used in the homogenate experiments. The higher alcohols produced by the homogenates were rapidly absorbed from the colon. We hypothesize that, when exposed to ethanol, the colonic flora produced toxic compounds which are absorbed and influence the body's response to ingested ethanol. Individual differences in this bacterial metabolism may account for the wide individual differences in susceptibility to ethanolrelated organ injury.Alcoholics vary in their susceptibility to ethanolrelated organ injury. For example, organ injury occurs in only a minority of heavy alcoholics and the damaged organ (e.g., liver, pancreas, nervous system, or heart) varies from patient to patient. A number of yet unproven hypotheses concerning individual differences in the metabolism of ethanol or its metabolic product, acetaldehyde, have been proposed to explain the differences in susceptibility to ethanol.The purpose of this report is to suggest another, apparently novel hypothesis which might help to explain some of the variable susceptibility to the ravages of ethanol-namely, that the metabolism of the colonic flora influences the host's response to ethanol. MATERIALS AND METHODSThe influence of ethanol on the metabolism of colonic bacteria was studied by comparing the metabolic products produced by human feces when incubated in the presence or absence of ethanol. Freshly passed human feces were homogenized anaerobically in pH 7.4, 0.1 A4 PO, buffered saline (1 part feces3 parts buffer). Twentymilliliter aliquots of this homogenate were then anaerobically incubated at 37°C with or without the addition of pure ethanol (0.1% v/v or 0.078 gm per dl).Our initial gas chromatographic analyses of the volatiles produced during incubation showed a multiplicity of compounds in the ethanol-treated homogenate which were not present in the homogenate incubated without ethanol. To date, we have identified and quantitated the alcohols accumulating in homogenates of feces obtained from 20 healthy subjects. Two-milliliter aliquots of the homogenates were removed at 0, 3, 6, and 24 hr of incubation and analyzed by gas chromatography-mass spectroscopy as follows. Two grams of K&O3 (I) were added to 2 ml homogenate in a 30-ml sealed vial using isobutyl alcohol as an internal standard. The mixture was heated at 70°C for 30 min, and 5 ml of the gas space was then analyzed for alcohols by gas chromatographymass spectroscopy using a Hewlett-Packard, Model 5992-B. A 25-pm silica capillary column containing Carbowax (20 M ) was employed at an initial temperature of 10°C for 1 min and then programmed to increase at 10°C per min...

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“…The various combinations of these subunits give rise to a large number of dimeric isoenzymes which differ with respect to their physicochemical and catalytic properties. An analysis of individual liver biopsies has shown that the isoenzyme pattern varies considerably from one individual to another (31). In addition to the variability of isoenzyme distribution, we have discovered a genetic variant of one subunit, which has been given the name 'atypical' human liver ADH (29).…”

mentioning

confidence: 99%

Metabolic Consequences of Alcohol Consumption

Wartburg¹

1977

Ann Nutr Metab

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The metabolic effects of alcohol are closely related to organic as well as societal aspects of alcoholism. Individual differences in the biologic sensitivity to ethanol are thought to represent important features underlying these afflictions. The results of recent biomedical research provide evidence for a biochemical individuality with respect to the enzymes involved in alcohol metabolism. Human liver alcohol dehydrogenase, the principle ethanol oxidizing enzyme in man, exists in multiple molecular forms (isoenzymes). In addition, a genetic polymorphism (‘atypical’ variant) is observed. Large racial differences are found for the prevalence of the variant enzyme, which is characterized by a high specific activity. Possible relationships of the individual isoenzyme pattern of alcohol dehydrogenase and of other alcohol metabolizing enzymes to the nature and extent of metabolic effects of ethanol are discussed.

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The Metabolism of Alcohol in Normals and Alcoholics: Enzymes

Cited by 43 publications

References 118 publications

Studies on the properties of the human alcohol dehydrogenase isozymes determined by the different loci ADH₁, ADH₂, ADH₃

Studies on the properties of the human alcohol dehydrogenase isozymes determined by the different loci ADH₁, ADH₂, ADH₃

Hypothesis: Metabolic Activity of the Colonic Bacteria Influences Organ Injury From Ethanol

Metabolic Consequences of Alcohol Consumption

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The Metabolism of Alcohol in Normals and Alcoholics: Enzymes

Cited by 43 publications

References 118 publications

Studies on the properties of the human alcohol dehydrogenase isozymes determined by the different loci ADH1, ADH2, ADH3

Studies on the properties of the human alcohol dehydrogenase isozymes determined by the different loci ADH1, ADH2, ADH3

Hypothesis: Metabolic Activity of the Colonic Bacteria Influences Organ Injury From Ethanol

Metabolic Consequences of Alcohol Consumption

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Product

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Studies on the properties of the human alcohol dehydrogenase isozymes determined by the different loci ADH₁, ADH₂, ADH₃

Studies on the properties of the human alcohol dehydrogenase isozymes determined by the different loci ADH₁, ADH₂, ADH₃