Microsomes, ethanol oxidizing activity

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. 

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. 

An example of a multi-enzyme complex is provided by MEOS (microsomal ethanol oxidizing system), which is composed of two different subunits with different enzyme activities. One subunit transfers electrons from NADPH to a cytochrome Fe-heme group on the 2nd subunit, which then transfers the electrons to O2. 

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). 

Both the microsomal ethanol oxidizing enzyme system and catalase activities were detected as early as 10 weeks of fetal age, and by contrast to alcohol dehydrogenase, no increases in activity were found during development. Cytochrome P-450 was detected at 13 weeks (Table III), and reached adult levels (Alvares et al., 1969) at 17 weeks of age. The activities of aniline hydroxylase obtained in four fetal livers were comparable to those reported in adult livers (Darby, 1970). The significant activities... 

In conlcusion, the rates of ethanol metabolism and the activity of hepatic alcohol dehydrogenase are both reduced in fetal life and in the newborn when compared with values obtained in the adult. Significant microsomal ethanol oxidizing system and catalase activities are detected early in fetal life and do not increase during further fetal development However, the contribution of these two enzymes to the m vivo metabolism of ethanol during development remains to be evaluated. 

Seitz, H.K., Korsten, M.A., Lieber, C.S. Ethanol oxidation by intestinal microsomes increased activity after chronic ethanol administration. Life Sci. 1979 25 1443-1448... 

The biosynthetic reactions involve a series of condensation processes and are distributed between cytosol and microsomes. All of the carbons of cholesterol are derived from acetyl-CoA, 15 from the methyl and 12 from the carboxyl carbon atoms. Acetyl-CoA is derived from mitochondrial oxidation of metabolic fuels (e.g., fatty acids) and transported to cytosol as citrate (Chapter 18) or by activation of acetate (e.g., derived from ethanol oxidation) by cytosolic acetyl-CoA synthase (Chapter 18). All of the reducing equivalents are provided by NADPH. 

Ethanol also inhibits ADH-catalyzed retinol oxidation in vitro, and ethanol treatment of mouse embtyos has been demonstrated to reduce endogenous RA levels. The inhibition of cytosolic RolDH activity and stimulation of microsomal RolDH activity could explain ethanol-mediated vitamin A depletion, separate from ADH isoenzymes. Although the exact mechanism of inhibition of retinoid metabolism by ethanol is unclear, these observations are consistent with the finding that patients with alcoholic liver disease have depletedhepatic vitamin A reserves [review see [2]. 

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