alcohol metabolism

Antonio Guia guia at CC.UManitoba.CA
Sun Feb 20 11:51:16 EST 1994

On Sat, 19 Feb 1994, Bernard Murray wrote:
> > On 18 Feb 1994, Paul Schlosser wrote:
> > > Drinking alcohol causes induction of cytochrome P450 2E1 (in the liver),
> > > a principle enzyme in alcohol metabolism.  So as your average consumption
> > > goes up, so does your metabolism.
> > That being the case, why do alcoholics get drunk on less alcohol than the
> > first time drinkers?
> Is this really a fact?  I assume that it could appear so if alcoholics
> maintained their blood alcohol level at a point where the addition of a
> small amount ("less than first time drinkers") would lead to a more profound
> clinical effect.  Also, it must be a little hard to differentiate between the
> Bernard Murray, Ph.D.

Although the kidneys certainly don't have a picnic, i think the most
profound clinical effect of alcoholism is hepatic cirrhosis, so alcohol
destroys the cells which detoxify it.  The cirrhosis is fatty in nature,
so once the cells are destroyed they will not be replaced (fat storages
grow inside the cells to the point where the nucleus becomes picnotic. 
The induction of the enzyme is rather quick, and in the absence of alcohol
the enzyme levels will return to normal.  Really this induction is only
significant in terms of the interaction that it may have on other drugs
being taken concurrently.  It may cause other drugs which can be
metabolized by this enzyme (and i don't think that P450 2E1 is the only
one) to be metabolized faster and therefore reach trough values lower than
required for therapeutic benefit.  With drugs of high thereapeutic index
even this is rather unimportant since one can just increase doseage.

The only lasting and cumulative effects of alcohol seem to reduce alcohol
metabolism rather than induce it.  To the alcoholic the first drink after
sobering up would probably meet with uninduced enzymes, and would
therefore be subject to a much lower first-pass effect through the liver,
therefore having a more prominant effect on the brain.

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