After caffeine, ethanol is the most commonly used recreational drug worldwide. Alcohol is synonymous with ethanol, and drinking often describes the consumption of beverages containing ethanol. In the United Kingdom (UK), a unit of alcohol (standard alcoholic drink; Table 1) contains 8 g of ethanol (ethyl alcohol). The Department of Health, the National Institute for Clinical Excellence (NICE), and several of the medical Royal Colleges in the UK have recommended sensible limits for alcohol intake based on these units of alcohol.

Table 1: Unit system of ethanol content of alcoholic beverages*
Beverage containing ethanol Units of ethanol
Half pint of low-strength beer (284 mls) 1
Pint of beer (568 mls) 2
500 ml of high-strength beer 6
Pint of cider 2
One glass of wine (125 mls) 1
Bottle of wine (750 mls) 6 - 10
One measure of spirits (e.g. whisky, gin, vodka) 1
Bottle of spirits (e.g. vodka 750 mls) 36
*The unit system is a convenient way of quantifying consumption of ethanol and offers a suitable means to give practical guidance. However, there are several problems with the unit system. The ethanol content of various brands of alcoholic beverages varies considerably (for example, the ethanol content of beers/ales is in the range 0.5–9.0% so a pint may contain 2–5 units) and the amounts of alcohol consumed in homes bear little in common with standard measures. Similarly, variations in the strength (9–14%) and serving size (125–250 ml or more) of wine makes quantization of self reported intakes rather difficult.


However, as the amount of ethanol in one unit or a standard alcoholic drink varies throughout the world (Table 2 and Table 3), the unit system does not allow international comparisons. Recommendations for sensible limits for alcohol intake also vary worldwide.

Table 2: Geographical variation in the amount of ethanol in one unit
Country Amount of ethanol (g)
Sweden 20
Japan 19.75
United States 14
Australia and New Zealand 10
United Kingdom 8

The unit system does not permit international comparisons.

Despite these guidelines, the quantity of alcohol consumed varies widely. Many enjoy the pleasant psychopharmacological effects of alcohol. However, some experience adverse reactions due to genetic variation of enzymes that metabolize alcohol. Misuse of alcohol undoubtedly induces pathological changes in most organs of the body. Some data have suggested that alcohol may be beneficial in the reduction of ischemic heart disease.

Many of the effects of alcohol correlate with the peak concentration of ethanol in the blood during a drinking session. It is therefore important to understand the factors that influence the blood ethanol concentration (BEC) achieved from a dose of ethanol.

Physical Properties of Ethanol

Ethanol is produced from the fermentation of glucose by yeast. Ethanol (Figure 1) is highly soluble in water due to its polar hydroxyl (OH) group. The nonpolar (C2H5) group enables ethanol to dissolve lipids and thereby disrupt biological membranes. As a relatively uncharged molecule, ethanol crosses cell membranes by passive diffusion.

Absorption and Distribution of Alcohol

The basic principles of alcohol absorption from the gastrointestinal (GI) tract and subsequent distribution are well understood. Beverages containing ethanol pass down the esophagus into the stomach. The endogenous flora of the GI tract can also transform food into a ‘cocktail0 containing several alcohols including ethanol. This is particularly important if there are anatomical variations in the upper GI tract (e.g. diverticulae).

Alcohol continues down the GI tract until absorbed. The ethanol concentration therefore decreases down the GI tract. There is also a concentration gradient of ethanol from the lumen to the blood. The concentration of ethanol is much higher in the lumen of the upper small intestine than in plasma (Table 4). Alcohol diffuses passively across the cell membranes of the mucosal surface into the submucosal space and then the submucosal capillaries.

Absorption occurs across all of the GI mucosa but is fastest in the duodenum and jejunum. The rate of gastric emptying is the main determinant of absorption because most ethanol is absorbed after leaving the stomach through the pylorus.

Alcohol diffuses from the blood into tissues across capillary walls. Ethanol concentration equilibrates between blood and the extracellular fluid within a single pass. However, equilibration between blood water and total tissue water may take several hours, depending on the cross-sectional area of the capillary bed and tissue blood flow.

Ethanol enters most tissues but its solubility in bone and fat is negligible. Therefore, in the postabsorption phase, the volume of distribution of ethanol reflects total body water. Thus, for a given dose, BEC will reflect lean body mass.

Metabolism of Alcohol

The rate at which alcohol is eliminated from the blood by oxidization varies from 6 to 10 g h1. This is reflected by the BEC, which falls by 9–20 mg dl1 h1 after consumption of ethanol. After a dose of 0.6–0.9 g per kg body weight without food, elimination of ethanol is approximately 15 mg dl blood1 h1. However, many factors influence this rate and there is considerable individual variation.

Absorbed ethanol is initially oxidized to acetaldehyde (Figure 2) by one of three pathways (Figure 3): 1. Alcohol dehydrogenase (ADH)–cystosol 2. Microsomal ethanol oxidizing system (MEOS)–endoplasmic reticulum 3. Catalase–peroxisomes

Alcohol Dehydrogenase

ADH couples oxidation of ethanol to reduction of nicotinamide adenine dinucleotide (NADþ) to NADH. ADH has a wide range of substrates and functions, including dehydrogenation of steroids and oxidation of fatty acids.

Alcohol Dehydrogenase Isoenzymes

ADH is a zinc metalloprotein with five classes of isoenzymes that arise from the association of eight different subunits into dimers (Table 5). These five classes of ADH are the products of five gene loci (ADH1–5). Class 1 isoenzymes generally require a low concentration of ethanol to achieve ‘half-maximal activity0 (low Km), whereas class 2 isoenzymes have a relatively high Km. Class 3 ADH has a low affinity for ethanol and does not participate in the oxidation of ethanol in the liver. Class 4 ADH is found in the human stomach and class 5 has been reported in liver and stomach. Whereas the majority of ethanol metabolism occurs in the liver, gastric ADH is responsible for a small portion of ethanol oxidation.


Peroxisomal catalase, which requires the presence of hydrogen peroxide (H2O2), is usually of little significance in the metabolism of ethanol. Metabolism of ethanol by ADH inhibits catalase activity because H2O2 production is inhibited by the reducing equivalents (NADH) produced by ADH. However, metabolism of ethanol by catalase may be more significant if the other pathways for ethanol metabolism are inhibited, for example, by mitochondrial damage in a chronic alcoholic.

Microsomal Ethanol Oxidizing System

Chronic administration of ethanol with nutritionally adequate diets increases clearance of ethanol from the blood. In 1968, the MEOS was identified. The MEOS has a higher Km for ethanol (8–10 mmol l1) than ADH (0.2–2.0 mmol l1) so at low BEC, ADH is more important. However, unlike the other pathways, MEOS is highly inducible by chronic alcohol consumption. The key enzyme of the MEOS is cytochrome P4502E1 (CYP2E1). Chronic alcohol use is associated with a 4- to 10-fold increase of CYP2E1 due to increases in mRNA levels and rate of translation.

Acetaldehyde Metabolism

Acetaldehyde is highly toxic but is rapidly converted to acetate. This conversion is catalyzed by aldehyde dehydrogenase (ALDH) and is accompanied by reduction of NADþ (Figure 3). There are several isoenzymes of ALDH (Table 6). The most important are ALDH1 (cytosolic) and ALDH2 (mitochondrial). The presence of ALDH in most tissues may reduce the toxic effects of acetaldehyde.

In alcoholics, the oxidation of ethanol is increased by induction of MEOS. However, the capacity of mitochondria to oxidize acetaldehyde is reduced. Hepatic acetaldehyde therefore increases with chronic ethanol consumption. A significant increase of acetaldehyde in hepatic venous blood reflects the high tissue level of acetaldehyde.

Metabolism of Acetate

The final metabolism of acetate derived from ethanol remains unclear. However, some important principles have been elucidated:

  1. The majority of absorbed ethanol is metabolized in the liver and released as acetate. Acetate release from the liver increases 21 2 times after ethanol consumption.
  2. Acetyl-CoA synthetase catalyzes the conversion of acetate to acetyl-CoA via a reaction requiring adenosine triphosphate. The adenosine monophosphate produced is converted to adenosine in a reaction catalyzed by 50-nucleosidase.
  3. Acetyl-CoA may be converted to glycerol, glycogen, and lipid, particularly in the fed state. However, this only accounts for a small fraction of absorbed ethanol.
  4. The acetyl-CoA generated from acetate may be used to generate adenosine triphosphate via the Kreb’s cycle.
  5. Acetate readily crosses the blood–brain barrier and is actively metabolized in the brain. The neurotransmitter acetylcholine is produced from acetyl-CoA in cholinergic neurons.
  6. Both cardiac and skeletal muscle are very important in the metabolism of acetate.

Based on these observations, future studies on the effects of ethanol metabolism should focus on skeletal and cardiac muscle, adipose tissue, and the brain.

Nonoxidative Metabolism of Alcohol

Nonoxidative metabolism of alcohol, which results in formation of ethyl esters from fatty acids occurs in several organs which lack an oxidative system to metabolize alcohol (e.g., pancreas, heart, and adipose tissue). These organs often develop alcoholinduced disease so fatty acid ethyl esters may play a role in the pathogenesis of the lesions induced by alcohol consumption. The nonoxidative metabolism of ethanol may be more significant if the other pathways for ethanol metabolism are inhibited.

Blood Ethanol Concentration

The relationship between BEC and the effects of alcohol is complex and varies between individuals and with patterns of drinking. Many of the effects correlate with the peak concentration of ethanol in the blood and organs during a drinking session. Other effects are due to products of metabolism and the total dose of ethanol ingested over a period of time. These two considerations are not entirely separable because the ethanol concentration during a session may determine which pathways of ethanol metabolism predominate.

It is of considerable clinical interest to understand what factors increase the probability of higher maximum ethanol concentrations for any given level of consumption.

Factors Affecting Blood Ethanol Concentration

Gender Differences in Blood Ethanol Concentration

Women achieve higher peak BEC than men given the same dose of ethanol per kilogram of body weight. The volume of distribution of ethanol reflects total body water. Because the bodies of women contain a greater proportion of fat, it is not surprising that the BEC is higher in women. However, gender differences in the gastric metabolism of ethanol may also be relevant.

Period Over which the Alcohol is Consumed

Rapid intake of alcohol increases the concentration of ethanol in the stomach and small intestine. The greater the concentration gradient, the faster the absorption of ethanol and therefore peak BEC. If alcohol is consumed and absorbed faster than the rate of oxidation, then BEC increases.

Effects of Food on Blood Ethanol Concentration

The peak BEC is reduced when alcohol is consumed with or after food. Food delays gastric emptying into the duodenum. This attenuates the sharp early rise in BEC seen when alcohol is taken on an empty stomach. Food also increases elimination of ethanol from the blood. The area under the BEC/time curve (AUC) is reduced (Figure 4). The contributions of various nutrients to these effects have been studied, but small, often conflicting, differences have been found. It appears that the caloric value of the meal is more important than the precise balance of nutrients.

In animal studies ethanol is often administered with other nutrients in liquid diets. The AUC is less when alcohol is given in a liquid diet than with the same dose of ethanol in water. The different blood ethanol profile in these models may affect the expression of pathology.

However, food increases splanchnic blood flow, which maintains the ethanol diffusion gradient in the small intestine. Food-induced impairment of gastric emptying may be partially offset by faster absorption of ethanol in the duodenum.

Beverage Alcohol Content and Blood Ethanol Concentration

The ethanol concentration of the beverage consumed (Table 7) affects ethanol absorption and can affect BEC. Absorption is fastest when the concentration is 10–30%. Below 10%, the low ethanol concentration in the GI tract reduces diffusion and the greater volume of liquid slows gastric emptying. Concentrations above 30% irritate the GI mucosa and the pyloric sphincter, increasing secretion of mucus and delaying gastric emptying. Some evidence has shown that even low concentrations of ethanol (e.g., 4%, as found in beer) may cause minor lesions in the gastric mucosa though they may be insignificant pathologically.

First-Pass Metabolism of Ethanol

The the area under the BEC/time curve (AUC) is significantly lower after oral dosing of ethanol than after intravenous or intraperitoneal administration. The total dose of intravenously administered ethanol is available to the systemic circulation. The difference between AUCoral and AUCiv represents the fraction of the oral dose that was either not absorbed or metabolized before entering the systemic circulation (first-pass metabolism (FPM)). The ratio of AUCoral to AUCiv reflects the oral bioavailability of ethanol.

The investigation of ethanol metabolism has primarily focused on the liver and its relationship to liver pathology. However, gastric metabolism accounts for approximately 5% of ethanol oxidation and 2–10% is excreted in the breath, sweat, or urine. The rest is metabolized by the liver.

After absorption, ethanol is transported to the liver in the portal vein. Some is metabolized by the liver before reaching the systemic circulation. However, hepatic ADH is saturated at a BEC that may be achieved in an average-size adult after consumption of one or two units. If ADH is saturated by ethanol entering the liver from the systemic circulation via the hepatic artery, ethanol in the portal blood must compete for binding to ADH. Although hepatic oxidation of ethanol cannot increase once ADH is saturated, gastric ADH can significantly metabolize ethanol at the high concentrations in the stomach after initial ingestion. If gastric emptying of ethanol is delayed, prolonged contact with gastric ADH increases FPM. Conversely, fasting, which greatly increases the speed of gastric emptying, virtually eliminates gastric FPM.

Physiological Effects of Alcohol

Ethanol or the products of its metabolism affect nearly all cellular structures and functions.

Effects of Alcohol on the Central Nervous System

Ethanol generally decreases the activity of the central nervous system. In relation to alcohol, the most important neurotransmitters in the brain are glutamate, gamma-aminobutyric acid (GABA), dopamine, and serotonin.

Glutamate is the major excitatory neurotransmitter in the brain. Ethanol inhibits the N-methyl-D-aspartate (NMDA) subset of glutamate receptors. Ethanol thereby reduces the excitatory effects of glutamate. GABA is the major inhibitory neurotransmitter in the brain. Alcohol facilitates the action of the GABA-a receptor, increasing inhibition. Changes to these receptors seem to be important in the development of tolerance of and dependence on alcohol.

Dopamine is involved in the rewarding aspects of alcohol consumption. Enjoyable activities such as eating or use of other recreational drugs also release dopamine in the nucleus accumbens of the brain. Serotonin is also involved in the reward processes and may be important in encouraging alcohol use.

The most obvious effects of ethanol intoxication on the central nervous system begin with behavior modification (e.g., cheerfulness, impaired judgement, and loss of inhibitions). These excitatory effects result from the disinhibition described previously (inhibition of cells in the brain that are usually inhibitory).

As a result of these effects, it is well recognized that operating vehicles such as cars or heavy machinery under the influence of ethanol is unsafe. However, the BEC after consumption of a specific amount of ethanol and the impairment caused by a specific BEC vary significantly between individuals. Despite this variation, BEC is used to define intoxication and provide a rough measure of impairment for legal purposes because it is an objective measurement that is difficult to contest.

Most countries have set maximum legally permissible BEC levels for drivers to reduce harm from ‘drink driving.’ Governments define these level after reviewing the available evidence. However, the definition of what is safe or acceptable varies between countries (Table 8). These BEC thresholds range from zero tolerance (0.0 mg ml1) to 0.8 mg ml1.

Some countries are considering the potential social benefits of lowering BEC limits. However, opponents cite factors such as the drinking culture, convenience, the unpalatability of tighter legislation and the impact on the alcohol industry.

The effects of ethanol are dose dependent (Table 9) and further intake causes agitation, slurred speech, memory loss, double vision, and loss of coordination. This may progress to depression of consciousness and loss of airway protective reflexes, with danger of aspiration, suffocation, and death.

This sequence of events is particularly relevant in the hospital setting, where patients may present intoxicated with a reduced level of consciousness. It is difficult to determine whether there is coexisting pathology such as an extradural hematoma or overdose of other drugs in addition to ethanol. Although measurement of BEC is helpful (Table 9), it is safest to assume that alcohol is not responsible for any disturbance in consciousness and to search for another cause.

Neuroendocrine Effects of Alcohol

Alcohol activates the sympathetic nervous system, increasing circulating catecholamines from the adrenal medulla. Hypothalamic– pituitary stimulation results in increased circulating cortisol from the adrenal cortex and can, rarely, cause a pseudo-Cushing’s syndrome with typical moon-shaped face, truncal obesity, and muscle weakness. Alcoholics with pseudo- Cushing’s show many of the biochemical features of Cushing’s syndrome, including failure to suppress cortisol with a 48-h low-dose dexamethasone suppression test. However, they may be distinguished by an insulin stress test. In pseudo-Cushing’s, the cortisol rises in response to insulin-induced hypoglycemia, but in true Cushing’s there is no response to hypoglycemia.

Ethanol affects hypothalamic osmoreceptors, reducing vasopressin release. This increases salt and water excretion from the kidney, causing polyuria. Significant dehydration may result particularly with consumption of spirits containing high concentrations of ethanol and little water. Loss of hypothalamic neurons (which secrete vasopressin) has also been described in chronic alcoholics, suggesting long-term consequences for fluid balance. Plasma atrial natriuretic peptide, increased by alcohol consumption, may also increase diuresis and resultant dehydration.

Alcoholism also affects the hypothalamic–pituitary–gonadal axis. These effects are further exacerbated by alcoholic liver disease. There are conflicting data regarding the changes observed. Testosterone is either normal or decreased in men, but it may increase in women. Estradiol is increased in men and women, and it increases as hepatic dysfunction deteriorates. Production of sex hormone-binding globulin is also perturbed by alcohol.

The development of female secondary sexual characteristics in men (e.g., gynecomastia and testicular atrophy) generally only occurs after the development of cirrhosis. In women, the hormonal changes may reduce libido, disrupt menstruation, or even induce premature menopause. Sexual dysfunction is also common in men with reduced libido and impotence. Fertility may also be reduced, with decreased sperm counts and motility.

Effects of Alcohol on Muscle

Myopathy is common, affecting up to two-thirds of all alcoholics. It is characterized by wasting, weakness, and myalgia and improves with abstinence. Histology correlates with symptoms and shows selective atrophy of type II muscle fibers. Ethanol causes a reduction in muscle protein and ribonucleic acid content. The underlying mechanism is unclear, but rates of muscle protein synthesis are reduced, whereas protein degradation is either unaffected or inhibited. Attention has focused on the role of acetaldehyde adducts and free radicals in the pathogenesis of alcoholic myopathy.

Alcohol and Nutrition

The nutritional status of alcoholics is often impaired. Some of the pathophysiological changes seen in alcoholics are direct consequences of malnutrition. However, in the 1960s, Charles Lieber demonstrated that many alcohol-induced pathologies, including alcoholic hepatitis, cirrhosis, and myopathy, are reproducible in animals fed a nutritionally adequate diet. Consequently, the concept that all alcohol-induced pathologies are due to nutritional deficiencies is outdated and incorrect.

Myopathy is a direct consequence of alcohol or acetaldehyde on muscle and is not necessarily associated with malnutrition. Assessment of nutritional status in chronic alcoholics using anthropometric measures (e.g., limb circumference and muscle mass) may be misleading in the presence of myopathy.

Acute or chronic ethanol administration impairs the absorption of several nutrients, including glucose, amino acids, biotin, folate, and ascorbic acid. There is no strong evidence that alcohol impairs absorption of magnesium, riboflavin, or pyridoxine, so these deficiencies are probably due to poor intakes. Hepatogastrointestinal damage (e.g., villous injury, bacterial overgrowth of the intestine, pancreatic damage, or cholestasis) may impair the absorption of some nutrients such as the fat-soluble vitamins (A, D, E, and K). In contrast, iron stores may be adequate as absorption is increased.

Effects of Alcohol on the Cardiovascular System

Alcohol affects both the heart and the peripheral vasculature. Acutely, alcohol causes peripheral vasodilatation, giving a false sensation of warmth that can be dangerous. Heat loss is rapid in cold weather or when swimming, but reduced awareness leaves people vulnerable to hypothermia. The main adverse effect of acute alcohol on the cardiovascular system is the induction of arrhythmias i.e., ‘Holiday Heart’. These are often harmless and experienced as palpitations but can rarely be fatal. Chronic ethanol consumption can cause systemic hypertension and congestive cardiomyopathy. Alcoholic cardiomyopathy accounts for up to one-third of dilated cardiomyopathies but may improve with abstinence or progress to death.

The beneficial, cardioprotective effects of alcohol consumption have been broadcast widely. This observation is based on population studies of mortality due to ischemic heart disease, case–control studies, and animal experiments. However, there is no evidence from randomized controlled trials. The apparent protective effect of alcohol may therefore result from confounding factors. For example, the diets are different to those of nondrinkers. Even the diets of beer drinkers are different from those of wine drinkers. Furthermore, on the population level, the burden of alcohol-induced morbidity and mortality far outweighs any possible cardiovascular benefit.

Effects of Alcohol on Liver Function

Fundamental to the effects of ethanol is the liver, in which 60–90% of ethanol metabolism occurs. Ethanol displaces many of the substrates usually metabolized in the liver. Metabolism of ethanol by ADH in the liver generates reducing equivalents. ALDH also generates NADH with conversion of acetaldehyde to acetate. The NADH:NADþ ratio is increased, with a corresponding increase in the lactate:pyruvate ratio. If lactic acidosis combines with a b-hydroxybutyrate predominant ketoacidosis, the blood pH can fall to 7.1 and hypoglycemia may occur. Severe ketoacidosis and hypoglycemia can cause permanent brain damage. However, in general the prognosis of alcohol-induced acidosis is good. Lactic acid also reduces the renal capacity for urate excretion. Hyperuricemia is further exacerbated by alcohol-induced ketosis and acetate mediated purine generation. Hyperuricemia explains, at least in part, the clinical observation that alcohol misuse can precipitate gout.

The excess NADH promotes fatty acid synthesis and inhibits lipid oxidation in the mitochondria, resulting in fat accumulation. Fatty changes within the liver are usually asymptomatic but can be seen on ultrasound or computed tomography scanning, and they are associated with abnormal liver toxicity tests (e.g., raised activities of serum g-glutamyl transferase, aspartate aminotransferase, and alanine transaminases). The supposition that most of the hepatic damage in alcoholism is due to increases in the NADH:NAD ratio per se is somewhat outdated. Now, molecular and cellular processes and acetaldehyde toxicity have been shown to be major contributors to the disease process.

Progression to alcoholic hepatitis involves invasion of the liver by neutrophils with hepatocyte necrosis. Giant mitochondria are visible and dense cytoplasmic lesions (Mallory bodies) are seen. Alcoholic hepatitis can be asymptomatic but usually presents with abdominal pain, fever, and jaundice, or, depending on the severity of disease, patients may have encephalopathy, ascites, and ankle edema.

Continued alcohol consumption may lead to cirrhosis. However, not all alcoholics progress to cirrhosis. The reason for this is unclear. It has been suggested that genetic factors and differences in immune response may play a role.

In alcoholic cirrhosis there is fibrocollagenous deposition, with scarring and disruption of surrounding hepatic architecture. There is ongoing necrosis with concurrent regeneration. Alcoholic cirrhosis is classically said to be micronodular, but often a mixed pattern is present. The underlying pathological mechanisms are complex and are the subject of debate. Induction of the MEOS and oxidation of ethanol by catalase result in free radical production. Glutathione (a free radical scavenger) is reduced in alcoholics, impairing the ability to dispose of free radicals. Mitochondrial damage occurs, limiting their capacity to oxidize fatty acids. Peroxisomal oxidation of fatty acids further increases free radical production. These changes eventually result in hepatocyte necrosis, and inflammation and fibrosis ensue. Acetaldehyde also contributes by promoting collagen synthesis and fibrosis.

Alcohol and Facial Flushing

Genetic variations in ADH and ALDH may explain why particular individuals develop some of the pathologies of alcoholism and others do not. For example, up to 50% of Orientals have a genetically determined reduction in ALDH2 activity (‘flushing0 phenotype). As a result, acetaldehyde accumulates after ethanol administration, with plasma levels up to 20 times higher in people with ALDH2 deficiency. Even small amounts of alcohol produce a rapid facial flush, tachycardia, headache, and nausea. Acetaldehyde partly acts through catecholamines, although other mediators have been implicated, including histamine, bradykinin, prostaglandin, and endogenous opioids.

This is similar to the disulfiram reaction due to the rise of acetaldehyde after inhibition of ALDH. Disulfiram is used therapeutically to encourage abstinence in alcohol rehabilitation programs. The aversive effects of acetaldehyde may reduce the development of alcoholism and the incidence of cirrhosis in ‘flushers.0 However, some alcoholics with ALDH2 deficiency and, presumably, higher hepatic acetaldehyde levels develop alcoholic liver disease at a lower intake of ethanol than controls.

Effects of Acetaldehyde

Acetaldehyde is highly toxic and can bind cellular constituents (e.g., proteins including CYP2E1, lipids, and nucleic acids) to produce harmful acetaldehyde adducts. Adduct formation changes the structure and the biochemical properties of the affected molecules. The new structures may be recognized as foreign antigens by the immune system and initiate a damaging response.

Adduct formation leads to retention of protein within hepatocytes, contributing to the hepatomegaly, and several toxic manifestations, including impairment of antioxidant mechanisms (e.g., decreased glutathione (GSH)). Acetaldehyde thereby promotes free radical-mediated toxicity and lipid peroxidation. Binding of acetaldehyde with cysteine (one of the three amino acids that comprise GSH) or GSH also reduces liver GSH content. Chronic ethanol administration significantly increases rates of GSH turnover in rats. Acute ethanol administration inhibits GSH synthesis and increases losses from the liver. Furthermore, mitochondrial GSH is selectively depleted and this may contribute to the marked disruption of mitochondria in alcoholic cirrhosis.

Effects of Acetate

The role of acetate in alcohol-induced pathology is not well understood. The uptake and utilization of acetate by tissues depend on the activity of acetyl-CoA synthetase. Acetyl-CoA and adenosine are produced from the metabolism of acetate. Acetate crosses the blood–brain barrier easily and is actively metabolized in the brain. Many of the central nervous system depressant effects of ethanol may be blocked by adenosine receptor blockers. Thus, acetate and adenosine may be important in the intoxicating effects of ethanol.

Ethanol increases portal blood flow, mainly by increasing GI tract blood flow. This effect is reproduced by acetate. Acetate also increases coronary blood flow, myocardial contractility, and cardiac output. Acetate inhibits lipolysis in adipose tissue and promotes steatosis in the liver. The reduced circulating free fatty acids (a source of energy for many tissues) may have significant metabolic consequences. Thus, some of the effects of alcohol may be due to acetate, though this area is under explored.


Alcohol dehydrogenase

Alcohol dehydrogenase (ADH) is an enzyme that couples oxidation of ethanol to reduction of nicotinamide adenine dinucleotide (NADþ) to NADH. ADH has a wide range of substrates and functions, including dehydrogenation of steroids and oxidation of fatty acids.

Aldehyde dehydrogenase

Aldehyde dehydrogenase (ALDH) is an enzyme that couples oxidation of acetaldehyde to reduction of NADþ. The presence of ALDH in tissues may reduce the toxic effects of acetaldehyde.

Blood ethanol concentration

Blood ethanol concentration is commonly used as a measure of intoxication. It is commonly expressed as mg l1, g dl1, or mmol l1.


Catalase is a common enzyme found in nearly all living organisms. The main action is the decomposition of hydrogen peroxide (H2O2) to water. It can also oxidize ethanol in a reaction that requires H2O2.

First-pass metabolism of ethanol

First-pass metabolism of ethanol reduces the concentration of ethanol before it reaches the systemic circulation.

Microsomal ethanol oxidizing system

The microsomal ethanol oxidizing system (MEOS) is another pathway of ethanol metabolism. The key enzyme of the MEOS is cytochrome P4502E1 (CYP2E1). This pathway requires oxidation of NADPH to NADPþ.

Further Reading

Department of Health (1995) Sensible Drinking: The Report of an Inter-Departmental Working Group. London: Department of Health.

Gluud C (2002) Endocrine system. In: Sherman DIN, Preedy VR, and Watson RR (eds.) Ethanol and the Liver. Mechanisms and Management, pp. 472–494. London: Taylor & Francis.

Haber PS (2000) Metabolism of alcohol by the human stomach. Alcoholism: Clinical & Experimental Research 24: 407–408.

Henderson L, Gregory J, Irving K, and Swan G (2003) The National Diet and Nutrition Survey: Adults aged 19–64 years. Energy, Protein, Carbohydrate, Fat and Alcohol Intake, Vol. 2. London: TSO.

Israel Y, Orrego H, and Carmichael FJ (1994) Acetate-mediated effects of ethanol. Alcoholism: Clinical & Experimental Research 18(1): 144–148.

Jones AW (2000) Aspects of in-vivo pharmacokinetics of ethanol. Alcoholism: Clinical & Experimental Research 24: 400–402.

Kwo PY and Crabb DW (2002) Genetics of ethanol metabolism and alcoholic liver disease. In: Sherman DIN, Preedy VR, and Watson RR (eds.) Ethanol and the Liver. Mechanisms and Management, pp. 95–129. London: Taylor & Francis.

Lader D and Meltzer H (2002) Drinking: Adults’ Behaviour and Knowledge in 2002. London: Office for National Statistics.

Lieber CS (2000) Alcohol: Its metabolism and interaction with nutrients. Annual Review of Nutrition 20: 395–430.

Mezey E (1985) Effect of ethanol on intestinal morphology, metabolism and function. In: Seitz HK and Kommerell B (eds.) Alcohol Related Diseases in Gastroenterology, pp. 342–360. Berlin: Springer-Verlag.

Morgan MY and Ritson B (2003) Alcohol and Health: A Handbook for Students and Medical Practitioners, 4th edn. London: Medical Council on Alcohol. National Institute for Health and Clinical Excellence (2008) Antenatal care: Routine care for the healthy pregnant woman. NICE clinical guideline 62.

Peters TJ and Preedy VR (1999) Chronic alcohol abuse: Effects on the body. Medicine 27: 11–15.

Rajendram R and Preedy VR (2005) Effect of Alcohol Consumption on the Gut. Digestive Diseases 23: 214–221.

Royal Colleges (1995) Alcohol and the heart in perspective. Sensible limits reaffirmed. A Working Group of the Royal Colleges of Physicians, Psychiatrists and General Practitioners. Journal of the Royal College of Physicians of London 29: 266–271.