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Page 6 of 16 Teschke. Hepatoma Res 2019;5:40 I http://dx.doi.org/10.20517/2394-5079.2019.0017

Figure 3. Microsomal metabolism of various chemicals including ethanol. At the level of cytochrome P450, metabolic drug-drug and
[15]
drug-ethanol interactions are feasible. Figure derived from a previous report

Figure 4. Hepatic microsomal cytochrome P450 and its interaction with substrates. Cytochrome P450 catalyzes the oxidation of
+
substrates such as drugs and ethanol, which bind to the ferric (3 ) iron of the cytochrome P450 as the initial metabolic step leading
[15]
finally to the oxidized substrate. The original figure was published in and derived from a recent article
Table 2. Potentially toxic metabolites resulting from enzymatic degradation of ethanol in the liver
Selected potentially toxic metabolites and reactive O 2 -species due to hepatic ethanol degradation
Acetaldehyde C 2 H 4 O
Ethoxy radical CH 3 CH 2 O •
Hydroxyethyl radical CH 3 C(•)HOH
Acetyl radical CH 3 CHO•
1
Singlet radical O 2
•
Superoxide radical HO 2
Hydrogen peroxide H 2 O 2
Hydroxyl radical HO •
Alkoxyl radical RO •
Peroxyl radical ROO •
Lipidperoxides
[15]
Derived from original reports and review articles as referenced in previous reports
[16]
ROS dependent products [Table 2] ; (4) part of the ROS will be used to metabolize ethanol or acetaldehyde
to reactive intermediates, whereby initially ethanol and acetaldehyde per se are not carcinogens but can
be classified as procarcinogens that are converted to ultimate carcinogens with the potential of inducing
AHCC by attacking DNA ; and (5) in addition, parts of ROS not used for MEOS would be freely available
[39]
for direct attack of DNA and could also trigger radical formation of soluble proteins and or phospholipids
or those located in structural membranes of liver cells organelles including mitochondria [8,15,16,18,33-36,39] .