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Letters to the Editor
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Alcohol metabolism
A different perspective
From Dr I. Ab I. Davies, MRPharmS
Far from attempting to create a problem (PJ, 31 January, p120),
I was offering an explanation for the conundrum presented in Pamela Mason’s
article PDF (100K), (PJ, 6 December 2003, p777), namely that
oral ingestion of a given dose of alcohol results in a higher blood alcohol
concentration
(BAC) in women than in men, whereas “following intravenous administration,
both men and women achieve similar blood alcohol levels, indicating that
other mechanisms may contribute to the difference in bioavailability
after oral intake”.
May I take this opportunity to put forward my argument from a different
perspective. If the difference in the body fat content between men and
women was responsible for the difference in BAC, one would expect to
see that reflected after intravenous administration as well as oral ingestion.
In a population of men and women of identical height and weight their
body mass indices (BMI) would be identical and under these circumstances,
by calculation, women would have approximately 10 per cent more body
fat than men and as a consequence a 10 per cent lower apparent volume
of distribution (Vd). However, by taking average body weights and heights
for men and women again the calculation of body fat only shows approximately
10 per cent difference between men and women but the Vd increases to
30 per cent. In both cases it should be possible to demonstrate a statistically
significant difference in BAC between men and women after intravenous
administration of an identical dose of alcohol.
Assuming the oral ingestion of one mole of alcohol and its distribution
in the liver, taking a mean aqueous volume in the region of one litre
for both men and women, the liver concentration would be approximately
1.0M (and after complete equilibration with body water in a 70kg man
a BAC of approximately l00mg/100ml). Since the Km (the concentration
at which the enzyme is working at half maximum rate) for alcohol dehydrogenase
is 1.0mM,1 degradation of the alcohol follows zero order kinetics and
is independent of alcohol concentration (assuming also an optimum concentration
of NAD+ [a co-factor in alcohol degradation]), but would be dependent
on the mass of enzyme present, which in the male liver would be approximately
25 per cent greater than in women. The presence of a higher concentration
of alcohol dehydrogenase in the kidney (cortex) and also in lung tissue
(the alveoli) together with that in the liver combined with the microsomal
cytochrome P450 oxidase — CYP45O2E1,2 would provide an explanation
for the zero order kinetics for the elimination of alcohol from the body
that is so useful in forensic work. However, at very low concentrations
of alcohol, its elimination is similar to that of most drugs and has
been reported to be exponential.3
Although alcohol might only be slightly miscible with (mono-, di- and
tri-) glycerides, it is infinitely miscible with phospholipids4 and is
able to interpolate into cellular membranes.5
I. ab I. Davies
Ballygowan, Co Down
References
1. Newsholme EA, Leech AR. Biochemistry for the medical sciences. Chichester:
John Wiley & Sons; 1985.
2. Gibson GG, Skett P. Introduction to drug metabolism, 2nd edition.
London: Blackie Academic Professional; 1994.
3. Williams RT. Detoxication mechanisms. London: Chapman & Hall Ltd;
1959.
4. Dawson RMC, Elliott DC, Elliott WH, Jones KM. Data for biochemical
research, 3rd edition. Oxford: Oxford University Press; 1986.
5. Murray RK, Granner DK, Mayes PA, Rodwell VW. Harper’s Biochemistry
22nd edition. London: Prentice Hall International (UK) Ltd; 1990. |
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