Effect of Ethanol on the Activity of Microsomal Enzymes

Abstract

Listen

Translate article

It is generally accepted that liver alcohol dehydrogenase (ADH), a soluble enzyme of the cytosol is responsible for ethanol oxidation in vivo. Furthermore, NADH generation (either by ethanol or acetaldehyde oxidation) offers a satisfactory explanation for a number of biochemical effects produced by ethanol, including increased lipogenesis (LIEBER, C.S. et al., 1959; LIEBER, C.S. and SCHMID, R., 1961; NIKKILA, E. and OJALA, K., 1963), decreased lipid oxidation (LIEBER, C.S. and SCHMID, R., 1961; LIEBER, C.S. et al., 1967), hyperlactacidemia (LIEBER, C.S. et al., 1962; LIEBER, C.S. and DAVIDSON, C.S., 1962), hyperuricemia (LIEBER, C.S. et al., 1962) and hypoglycemia, discussed by others in this symposium. More recent studies, however, indicate that in addition to ADH, liver microsomes, which comprise the smooth endoplasmic reticulum (SER), are also capable of oxidizing ethanol (LIEBER, C.S. and DECARLI, L.M., 1968; 1970a). This microsomal ethanol oxidizing system (MEOS) differs strikingly from ADH. As illustrated in Figure 1, NADPH instead of NAD is required. Even acetylpyridineNAD, which enhances liver ADH activity (KAPLAN, N.O. et al., 1956) was ineffective. Optimum pH for MEOS is 6.8–7.4 instead of 10 to 11 for ADH. ADH and MEOS can also be differentiated by the effects of pyrazole: at 2mM, pyrazole completely inhibited ADH activity, but reduced that of MEOS by only 11 percent (LIEBER, C.S. and DECARLI, L. M., 1970a). At that concentration, pyrazole decreased ethanol metabolism in rat liver slices by 76 percent. If results of enzyme assays are applicable to liver slice metabolism, and if one can extrapolate from slices to in vivo conditions, these results may indicate that normally, two-thirds to three-quarters of the ethanol is metabolized via ADH and one-fourth to one-third via an alternate system, most likely MEOS.