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Teschke. Hepatoma Res 2019;5:40 I http://dx.doi.org/10.20517/2394-5079.2019.0017 Page 5 of 16

Figure 2. Constituents of the microsomal ethanol-oxidizing system

Table 1. MEOS and its cytochrome P450 isoforms
Cytochrome P450 isoforms MEOS activity/cytochrome P450
1A2 10.90
2A6 3.75
2B6 2.89
2D6 0.70
2E1 11.51
A4 3.38
To assess the turnover number, MEOS activity as nmoles acetaldehyde/min is
calculated per nmoles cytochrome P450, all expressed per mg of microsomal
protein. Compilation achieved by data extraction from a report of Asai et al. [32]

and phospholipids without their yet clearly determined place of interaction [Figure 2], as early recognized
[21]
during isolation of MEOS [Figure 1] , with ROS production and ethanol oxidation carried out by the
three components [8,15,16,18] . Separated from ADH and catalase activities shown on the left side of the
elution pattern, MEOS activity was recovered in eluates on the right side containing all three microsomal
constituents: cytochrome P450, NADPH-cytochrome c reductase (better to be analyzed as compared to
[21]
NADPH cytochrome P450 reductase), and microsomal phospholipids .

[22]
Using our published elution procedure of a stepwise KCl gradient , a subsequent report reaffirmed the
[28]
[22]
validity and reproducibility of our initial results in all details , as published before . This reassured our
proposed participation of special microsomal enzymes and constituents in MEOS and its independence
from ADH and catalase. The participation and obligatory role of these three components for MEOS was
later verified using purified microsomal constituents in order to reconstitute MEOS [29,30] , in support by
other studies showing the direct oxidation of ethanol by a catalase-free and alcohol dehydrogenase-free
reconstituted system containing cytochrome P-450 . Therefore, a close association between ROS and
[31]
MEOS exists, to be further discussed in relation to carcinogenicity and AHCC.

Reactive oxygen species
New sophisticated analytical techniques were developed that helped characterize MEOS, CYP isoforms
with preference of microsomal CYP 2E1, and ROS [4,8,15,16,18,32-36] . One of the highlights was the observation
in humans that MEOS consists of several CYP isoforms with CYP 2E1 as the most active in microsomal
[32]
ethanol oxidation , with variable turnover numbers of MEOS activity if calculated per CYP isoform
content [Table 1] .
[32]

With focus on the hepatic microsomal CYP 2E1, a variety of phenomena can now be explained, as
illustrated with a few examples [8,15,16,19-21,28,32-39] : (1) prolonged alcohol consumption upregulates the
NADPH and oxygen dependent MEOS activity [19-21,37,38] that adaptively enhances the overall metabolism
of ethanol [36,37] through an increase of CYP 2E1 [29,33] ; (2) in the presence of NADPH and molecular oxygen,
CYP 2E1 metabolizes not only ethanol in the context of MEOS but also many other exogenous substrates
[16]
with metabolic competitive interactions at the level of CYP [Figure 3] ; (3) during CYP 2E1 dependent
[16]
reactions, oxygen split often is incomplete [Figure 4] , allowing the generation of various types of ROS and