General interest question / alcohol metabolism

Stephen Marshall marshall at kauri.vuw.ac.nz
Mon Feb 21 16:51:34 EST 1994


In article <Pine.3.05.9402201047.A3789-9100000 at ccu.umanitoba.ca>,
guia at CC.UManitoba.CA (Antonio Guia) wrote:

> On 20 Feb 1994 mail_boot at uqvax.cc.uq.oz.au wrote:
> > > On 18 Feb 1994, Paul Schlosser wrote:
> > >> Drinking alcohol causes induction of cytochrome P450 2E1 (in the liver),
> > > That being the case, why do alcoholics get drunk on less alcohol than the
> > > first time drinkers?
> > They don't. 
> > ROBERT BOOT                                             R.BOOT at cc.uq.edu.au
> 
> so what effect would liver dammage have?
> 
> -tg

[lecture mode on]

Consumption of alcohol over a medium to long period of time results in a
variety of histological and metabolic changes to human liver. Microsomal
systems capable of oxidising alcohol to acetaldehyde are induced (they are
not specific to alcohol by the way, which can cause problems with the
metabolism of other drugs). There may also be a short term induction of
Alcohol Dehydrogenase activity. Initially the capacity to oxidise ethanol
increases, however with continued abuse of alcohol, fat infiltrates the
liver, fibrosis and cirrhosis occur and liver function becomes impaired,
leading to a reduction in alcohol oxidation.

There is a lot of variation in individual capacity to metabolise ethanol,
some of this is probably related to variation in alcohol and aldehyde
dehydrogenase, other reasons could include body water distribution and
variation in other systems like the cytochromes. Other systems suggested to
metabolise ethanol include Catalase (limited by supply of H2O2) and Fatty
Acid Ethyl Ester Synthase. The differences between men and women appear to
have two components - differences in body water distribution, and variation
in Gastric ADH expression.

Interestingly, alcoholics treated with antabuse (disulfiram - an inhibitor
of aldehyde dehydrogenase) find that they need to drink less alcohol in
order to get the same "high" they normally get from much more alcohol.
Given the toxic effects of acetaldehyde (and disulfiram) this is probably
not a good way to reduce spending on alcohol 8-)

[lecture mode off]

basically the system is _very_ complicated and blanket statements rarely
hold true. 8-)

Stephen
-- 
Macintosh Consultant                              Marshall at kauri.vuw.ac.nz
(also PhD student studying alcohol metabolism 8-)
Victoria University of Wellington
New Zealand



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