Metabolism ethanol

Ethanol (EtOH, alcohol ) naturally occurs in fruit in small quantities. Alcoholic drinks contain much higher concentrations. Their alcohol content is usually given as percent by volume. To estimate alcohol uptake and the blood alcohol level, it is useful to convert the amount to grams of ethanol (density 0.79 kg L ). For example, a bottle of beer (0.5 L at 4% v/v alcohol) contains 20 mb = 16 g of ethanol, while a bottle of wine (0.7 L at 12% v/v alcohol) contains 84 ml = 66 g ethanol. 

Ethanol is membrane-permeable and is quickly resorbed. The maximum blood level is already reached within 60-90 min after drinking. The resorption rate depends on various conditions, however. An empty stomach, a warm drink (e.g., mulled wine), and the presence of sugar and carbonic acid (e.g., in champagne) promote ethanol resorption, whereas a heavy meal reduces it. Ethanol is rapidly distributed throughout the body. A large amount is taken up by the muscles and brain, but comparatively little by adipose tissue and bones. Roughly 70% of the body is accessible to alcohol. Complete resorption of the ethanol contained in one bottle of beer (16 g) by a person weighing 70 kg (distribution in 70 kg 70/100 = 49 kg) leads to a blood alcohol level of 0.33 per thousand (7.2 mM). The lethal concentration of alcohol is approximately 3.5 per thousand (76 mM). 

The rate of ethanol degradation in the liver is limited by alcohol dehydrogenase activity. The amount of NAD available is the limiting factor. As the maximum degradation rate is already reached at low concentrations of ethanol, the ethanol level therefore declines at a constant rate (zero-order kinetics). The calorific value of ethanol is 29.4 kj g Alcoholic drinks—particularly in alcoholics—can therefore represent a substantial proportion of dietary energy intake. 

Alcohol is a socially accepted drug of abuse in Western countries. Due to the high potential for addiction to develop, however, it is actually a hard drug and has a much larger number of victims than the opiate drugs, for example. In the brain, ethanol is deposited in membranes due to its amphipathic properties, and it influences receptors for neurotransmitters (see p. 352). The effect of GABA is enhanced, while that of glutamate declines. 

High ethanol consumption over many years leads to liver damage. For a healthy man, the limit is about 60 g per day, and for a woman about 50 g. However, these values are strongly dependent on body weight, health status, and other factors. 

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As regards toxicity, pyrazole itself induced hyperplasia of the thyroid, hepatomegaly, atrophy of the testis, anemia and bone marrow depression in rats and mice (72E1198). The 4-methyl derivative is well tolerated and may be more useful than pyrazole for pharmacological and metabolic studies of inhibition of ethanol metabolism. It has been shown (79MI40404) that administration of pyrazole or ethanol to rats had only moderate effects on the liver, but combined treatment resulted in severe hepatotoxic effects with liver necrosis. The fact that pyrazole strongly intensified the toxic effects of ethanol is due to inhibition of the enzymes involved in alcohol oxidation (Section 4.04.4.1.1). 

Ethanol metabolism occurs mainly in the liver and proceeds by oxidation in two steps, first to acetaldehyde (CHjCHO) and then to acetic add (CH3CO2H)- When continuously present in the body, ethanol and acetaldehyde are toxic, leading to the devastating physical and metabolic deterioration... 

Alcohol dehydrogenase is a cytoplasmic enzyme mainly found in the liver, but also in the stomach. The enzyme accomplishes the first step of ethanol metabolism, oxidation to acetaldehyde, which is further metabolized by aldehyde dehydrogenase. Quantitatively, the oxidation of ethanol is more or less independent of the blood concentration and constant with time, i.e. it follows zero-order kinetics (pharmacokinetics). On average, a 70-kg person oxidizes about 10 ml of ethanol per hour. 

Catalase is a hver enzyme that uses hydrogen peroxide to oxidize other substances. In vivo, the catalase system does not play a significant role in ethanol metabolism, probably because the quantities of hydrogen peroxide available are insufficient for ethanol metabolism. 

The microsomal ethanol oxidizing system is another mechanism of ethanol metabolism. CYP2E1 may be an important enzyme in the metabolism of ethanol in heavy drinkers, who may have a 10-fold increase in activity. Two aUehc variants in the gene cl and c2) are associated with differing enzymatic activity. Approximately 40% of Japanese have the more active c2 allele, which is rare in individuals of European heritage (Sun et al. 2002). It is not believed to be a risk or protective factor in the development of alcohohsm, although current studies are examining its relationship to a variety of ethanol-related diseases. 

Sun F, Tsuritani 1, Yamada Y Contribution of genetic polymorphisms in ethanol-metabolizing enzymes to problem drinking behavior in middle-aged Japanese men. Behav Genet 32 229—236, 2002... 

Iturriage, H., Ugarte, H. and Israel, Y, (1980). Hepatic vein oxygenation, liver blood flow and the rate of ethanol metabolism in recently abstinent alcoholic patients. Eur. J. Clin. Invest. 10, 211-218. 

Rajasinghe, H., Jayatilleke, E. and Shaw, S. (1990). DNA cleavage during ethanol metabolism, role of superoxide radicals and catalytic iron. Life Sci. 47, 807-814. 

Liver metabolism is affected by methylxanthines. In high doses, theophylline and caffeine increase the level of cyclic AMP. Very high levels of methylxanthines decrease the level of branched chain and aromatic amino acids in plasma. Coffee appears to have little effect on ethanol metabolism. 

The metabolism of most drugs or chemicals is proportional to the concentration in the blood, which allows a half-life to be calculated. Ethanol is different its metabolism is relatively constant over time and does not increase with rising blood ethanol concentrations. Metabolism is proportional to body weight thus the bigger you are, the higher the rate of ethanol metabolism, but on average ethanol is metabolized at a rate of 120 mg/kg per hour or about 1 oz (30 ml) in 3 hours. 

F. The electrons that are generated from the first step in ethanol metabolism (catalyzed by alcohol dehydrogenase) are transported into the mitochondrion by these two shuttles. 

Treatment for severe ethanol overdose is generally supportive. Increased intracranial pressure can be relieved by intravenous administration of hypertonic mannitol. Hemodialysis can accelerate the removal of ethanol from the body. Stimulants of ethanol metabolism, such as fructose, are not sufficiently effective, and use of analeptics is not recommended because of the possibility of precipitating convulsions. 

During chronic alcohol consumption, MEOS activity is induced. As a result, chronic alcohol consumption results in significant increases not only in ethanol metabolism but also in the clearance of other drugs eliminated by the cytochrome P450s that constitute the MEOS system, and in the generation of the toxic byproducts of cytochrome P450 reactions (toxins, free radicals, H202). 

Acetaldehyde is oxidized to acetic acid by NAD+-dependent aldehyde dehydrogenases (ALDH) in liver and nasal mucosal preparations. Its administration to rats causes an increase in urinary excretion of sulfur metabolites and it is known to react with cysteine to produce a thiazolidine 4-carboxylic acid derivative that can be A -nitro-sated in vivo upon co-administration of nitrite (lARC, 1985). Many studies have been published subsequently, but these have been mainly in the context of ethanol metabolism. 

Jones MK, Jones BM. Ethanol metabolism in women taking oral contraceptives. Alcohol Clin Exp Res 1984 8(l) 24-8. 

Schoedel KA, Tyndale RF. Induction of nicotine-metabolizing CYP2B1 by ethanol and ethanol-metabolizing CYP2E1 by nicotine summary and implications. Biochim Biophys Acta. 2003 1619 283-290. 

A significant amount of ethanol metabolism by gastric ADH occurs in the stomach in men, but a smaller amount occurs in women, who appear to have lower levels of the gastric enzyme. This difference in gastric metabolism of alcohol in women probably contributes to the sex-related differences in blood alcohol concentrations noted above. 

Several other drugs, eg, metronidazole, certain cephalosporins, sulfonylurea hypoglycemic drugs, and chloral hydrate, have disulfiram-like effects on ethanol metabolism. Patients should be warned to avoid drinking ethanol while taking these drugs and for several days after they discontinue them. 

What are the metabolic products of ethanol oxidation in the body How does the rate of ethanol metabolism compare to that of methanol metabolism ... 

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