Good question - the answer is that ALDH deficient
individuals (and alcoholics treated with disulfiram)
develop high acetaldehyde levels on very low doses of
alcohol, and consequently suffer the full monty of a
hang-over: reportedly very unpleasant! So they quickly learn
that even a few sips is too much: there is no social
pay-off. For this reason, disulfuram is not all that
successful, because compliance is very low.
A parallel is giving azathioprine to patients deficient in
thiopurine methyltransferase (TPMT): normal or half doses
can kill; these patients can tolerate doses only up to 1/20
normal.
I guess these examples show the importance of flux through
metabolic pathways: a blockage rapidly causes metabolic
'overflow' or overdose. Hence the wide interest in the
developing field of pharmacogenetics.
----------------------
Dr John A Duley
Purine Research Laboratory
Guy's Hospital
London SE1 9RT (GB)
-----------------------------------
On Wed, 4 Dec 2002 08:46:11 -0000 "Robertson, Stuart"
<[log in to unmask]> wrote:
> John,
> Why is it thought that acetaldehyde is responsible for the addictive aspects
> of ethanol, when the basis for aversion therapy in alcoholics (disulfiram)
> is based on inhibition of ALDH and production of acetaldehyde if alcohol is
> ingested?
> Also, individuals who are alcohol intolerant due to inherited ALDH
> deficiency do not become addicted do they?
> Am I missing something obvious?
>
> Stuart Robertson
> Clinical Biochemistry Dept
> Hull Royal Infirmary
> Hull
> HU3 2JZ
>
> > ----------
> > From: Dr John A Duley[SMTP:[log in to unmask]]
> > Reply To: [log in to unmask]
> > Sent: 03 December 2002 18:35
> > To: [log in to unmask]
> > Subject: Re: alcohol intolerance
> >
> > ........Acetaldehyde is vasodilative and produces a
> > characteristic 'flushing syndrome' (this would help for
> > diagnosis of the patient).
> >
> > It also produces headache etc. It is thought to be
> > responsible for the addictive aspects of alcohol........
> >
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