Microsomes, ethanol oxidizing

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. 

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. 

In addition to alcohol dehydrogenase, ethanol can be oxidized to acetaldehyde by the microsomal mixed-function oxidase system (cytochrome P450 2 El), as illustrated in Figure 35.1. Although this microsomal ethanol-oxidizing system probably has minor impor-... 

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. 

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. 

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. 

Ekstrom G, von Bahr C, Ingelman-Sundberg M. Human liver microsomal cytochrome P-450IIE1. Immunological evaluation of its contribution to microsomal ethanol oxidation, carbon tetrachloride reduction and NADPH oxidase activity. Biochem Pharmacol 1989 38 689-693. 

The induction of liver enzymes has been demonstrated in many species, including humans, and probably represents a homeostatic, defense mechanism. Induction usually requires multiple exposures to the inducing agent over a period of several days, the time required for the synthesis of new protein. Enzymes induced include the cytochrome P450 monooxygenase system glucuronyltransferase the microsomal ethanol oxidative system and the steroid-metabolizing system. 

Lieber CS. The discovery of the microsomal ethanol oxidizing system and its physiologic and pathologic role. Drug Metab Rev 2004 36 511-529. 

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)...

A second pathway of alcohol oxidation becomes importarit with consumption of large amounts of alcohol or with chronic alcoholism. This pathway, called the ethanol-oxidizing system of the ER, involves the heme enzyme cytochrome F450 and one other protein. Cytochrome r450 alone cannot catalyze the oxidation. As homogenization of the liver results in disruption of the HR to form tiny vesicles called microsomes, the system has also been called the microsomal ethanol-oxidizing system. 

Methylcobalamin, 516 5-Melhyl-cytosine, deaminatitm, 894 Methylglyoxal, 836 Methylmalonic acid (MMA), 434, 522 MethylmalcHiy. CoA, 434, 517, 518 Mevalonic acid, 327, 328 Mg-ATP complex, 795-796 Micelles, 25,27-29 MLcroaulophagy, 444 Microbiological assays, 508 biotin determination, 541 folate status by, 509 thiamin status, 607 Microcytic anemia, 5H Microsomal ethanol-oxidizing system, 247 Microvilli, 58 Milk... 

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. 

MEOS microsomal ethanol oxidizing system ALDH aldehyde dehydrogenase THF tetrahydrofolate. 

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... 

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