MEOS, microsomal ethanol oxidizing system

Microsomal ethanol oxidizing system (MEOS) + NADPH... 

Ethanol is oxidized by alcohol dehydrogenase (in the presence of nicotinamide adenine dinucleotide [NAD]) or the microsomal ethanol oxidizing system (MEOS) (in the presence of reduced nicotinamide adenine dinucleotide phosphate [NADPH]). Acetaldehyde, the first product in ethanol oxidation, is metabolized to acetic acid by aldehyde dehydrogenase in the presence of NAD. Acetic acid is broken down through the citric acid cycle to carbon dioxide (CO2) and water (H2O). Impairment of the metabolism of acetaldehyde to acetic acid is the major mechanism of action of disulfiram for the treatment of alcoholism. 

Metabolism of ethanol by alcohol dehydrogenase and the microsomal ethanol-oxidizing system (MEOS). Alcohol dehydrogenase and aldehyde dehydrogenase are inhibited by fomepizole and disulfiram, respectively. NAD +, nicotinamide adenine dinucleotide NADPH, nicotinamide adenine dinucleotide phosphate. 

Ethanol is not metabolized by cytochrome P-450 enzymes (microsomal drug-metabolizing systems, or MEDS). However, it is metabolized to a certain extent by the microsomal ethanol-oxidizing system (MEOS). 

Lieber CS. Microsomal ethanol-oxidizing system (MEOS) the first 30 years (1968-1998)—a review. Alcohol Clin Exp Res 1999 23 991-1007. 

The second pathway for ethanol metabolism is called the ethanolinducible microsomal ethanol-oxidizing system (MEOS). This cytochrome P450-dependent pathway (Section 26.4.2) generates acetaldehyde and subsequently acetate... 

Fig. 3.16 Diagram showing alcohol degradation in the liver cell by means of alcohol dehydrogenase (ADH), catalase and the microsomal-ethanol oxidizing system (MEOS) as well as by aldehyde dehydrogenase (ALDH)...

Although the major metabolic pathway for ethanol is via alcohol dehydrogenase (see below) there is also a microsomal ethanol oxidizing system (MEOS) which metabolizes ethanol to ethanal. The mechanism may involve hydroxylation at the carbon atom, although this is uncertain. Although this enzyme system is of minor importance in naive subjects, exposure to ethanol can induce the enzyme system such that it becomes the major enzyme system metabolizing ethanol. 

Ingested alcohol is metabolized to acetaldehyde mainly by the action of liver alcohol dehydrogenase. Catalase (21,22), the microsomal ethanol oxidizing system (MEOS) (23-25), and extrahepatic pathways have also been considered as ethanol metabolizers, but these systems probably play only a minor role in most cases (for a detailed discussion of ethanol metabolism, see review by Hawkins and Kalant, 26). Ethanol metabolism produce an increase in the NADH/NAD+ ratio in the liver... 

The other principal route of ethanol oxidation in the liver is the microsomal ethanol oxidizing system (MEOS), which also oxidizes ethanol to acetaldehyde (Fig. 25.3). The principal microsomal enzyme involved is a cytochrome P450 mixed-function oxidase isozyme (CYP2E1), which uses NADPH as an additional electron donor and O2 as an electron acceptor. This route accounts for only 10 to 20% of ethanol oxidation in a moderate drinker. 

They are all found in the smooth endoplasmic reticulum and are referred to as microsomal enzymes (for example, CYP2E1 is also referred to as the microsomal ethanol oxidizing system, MEOS). 

Microsomal ethanol-oxidizing system (MEOS) At blood ethanol levels below 100 mg/dL, this liver microsomal mixed-function oxidase system contributes little to ethanol metabolism. However, the MEOS increases in activity with chronic exposure to ethanol or to inducing agents such as barbiturates, and this increase may be partially responsible for the development of tolerance. 

The microsomal ethanol-oxidizing system (MEOS) becomes significant in terms of ethanol metabolism only at blood levels in excess of 100 mg/dL. Chronic exposure to ethanol increases the activity of MEOS, and this effect may be contributory to metabolic tolerance. None of the other enzymes involved in ethanol metabolism change their activities with chronic use. Ethanol induces the formation of certain cytochrome P450 isozymes if used regularly. The answer is (C). 

Figure 7.85 The metabolism of methanol. Abbreviations. ADH, alcohol dehydrogenase MEOS, microsomal ethanol-oxidizing system ALDH, aldehyde dehydrogenase THF, tetrahydrofolate.

MEOS microsomal ethanol oxidizing system, mercapto- — SH group, metallothionein metal-binding protein, methylation addition of a methyl group. 

MEOS microsomal ethanol oxidizing system ALDH aldehyde dehydrogenase THF tetrahydrofolate. 

The multienzyme complex MEOS (microsomal ethanol oxidizing system), which is also called cytochrome P450-2E1, provides an additional route for ethanol oxidation to acetaldehyde in the liver. 

Chronic ingestion of ethanol has increased the content of MEOS, the microsomal ethanol oxidizing system, in Al Martini s liver. MEOS is a cytochrome P450 enzyme that catalyzes the conversion of ethanol, NADPH and O2 to acetaldehyde, NADP, and 2 H2O (see Chapter 9). The adjective microsomal is a term derived from experimental cell biology that is sometimes used for processes occurring in the ER. When cells are lysed in the laboratory, the ER is fragmented into vesicles called microsomes, which can be isolated by centrifugation. Microsomes, as such, are not actually present in cells. 

Figure 29.3 Summary diagram of major impacts of ethanol on metabolic pathways. An influx of ethanol disturbs the balance of carbohydrate and fatty acid metabolism. As a result of the oxidation of ethanol, concentrations of NADH and acetyl CoA are increased. Steps in the tricarboxylic acid cycle (TCA) and the mitochondrial pathway for p-oxidatlon of free fatty acids (FFA) which produce these species are inhibited (blue). At the same time, the excess amounts of NADH and acetyl CoA create conditions in which the fatty add synthesis and acidosis are favoured (red). The abundance of acetyl CoA means alcohol precursor metabolites accumulate. See text for a detailed explanation. Abbreviations ADH, alcohol dehydrogenase MEOS, microsomal endoplasmic oxidising system ALD, aldehyde dehydrogenase TG, triglycerides TCA, tricarboxylic acid cycle FFA, free fatty adds.

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