Transcript Catchy rubrik

The involvement of ADH in Alcohol Intolerance
Poster project - Biokemi 1 – 2009
Andy Vincent & Johan Dunevall
Institutionen för kemi, Göteborgs Universitet
Box 462, 405 30 Göteborg (Sverige)
Summery
Alcohol intolerance is a genetic condition caused by the polymorphism in the genes encoding the
enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). In afflicted individuals
ADH2 has been attributed as an over active enzyme that increases the levels of the toxin
acetealdehyde through the oxidation of ethanol, which causes physilogical reactions such as facial
flushing.
Inltroduction
Metabolism
Alcohol intolerance can have several
meanings depending on how the alcohol
has come into contact with the body. Skin
related allergies and rashes are results of
exposure to alcohol through contact of
the skin but here the effects of alcohol
intolerance
is
focused
on
the
consumption of ethanol. The major
symptom of the intolerance is facial
flushing due to blood vessel vasodilation
(Eriksson, 2001), the result of the
consumption of small amounts of
alcoholic beverages. Alcohol flushing
after light drinking is triggered mainly by
severe acetaldehydemia (Yokoyama,
2003). This effect is experienced in large
groups of Asian populations but has also
been seen to a lesser extent in Western
populations. Other effects of alcohol
consumption in the affected individual
can be nausea, headaches, and
occasional skin swelling and itchiness.
The oxidation of ethanol to acetate is a two step
process catalyzed by two enzymes. The first step is the
oxidation of ethanol to acetaldehyde catalyzed by
alcohol dehydrogenase. The second step is the further
oxidation to acetate by aldehyde dehydrogenase. In
both of these reactions NAD+ is reduced to NADH to
balance the redox reaction. The rate of alcohol
oxidation is the crucial factor that determines the
metabolic consequences during alcohol intoxication. A
defect in one or both of these enzymes would cause
high levels of toxic acetaldehyde.
Facial flushing: the before
and after picture of an Asien
individual that consumed
alcohol.
Genetic information
ADH: the structure of the
enzyme, with a substrate
analog shown in green.
Although ADH participates in the effects of alcohol intolerance, the relevance of the ADH for the
actions of alcohol is not documented as much as with ALDH. ADH has more than 20 different
isoenzymes with greatly differing kinetic properties in vitro (Sherman). On chromosome 4, the
enzyme is encoded by three adjacent gene loci, ADH1, ADH2, and ADH3. The kinetic
differences among ADH2 isozymes are more evident than those of the ADH3 isozymes, where
the alcohol-intolerant individual would have a more active ADH2 isozyme, increasing the levels
of acetaldehyde. So it is probable that a defect in ADH2 is a partial cause of the intolerance.
Many Asians lack enzyme activity of ALDH2 and have highly active enzyme activity of ADH2,
attributed to point mutations within both structural genes (Anonymous, 2003). Hence, the
expression of these two enzyme mutations could determine the alcohol tolerance among Asian
populations.
Referenser
Anonymous. (2003). Diabetic Vasculopathy and Alcohol Tolerance Trait in Type 2 Diabetes. diabetes care, volume 26, number 1 , 246.
Eriksson, C. J. (2001). Functional Relevance of Human ADH Polymorphism. alcoholism: clinical and experimental research , 1578.
Sherman, D. I. (u.d.). Association ofrestriction fragment length polymorphism in alcohol.
Yokoyama, T. (2003). Alcohol Flushing, Alcohol and Aldehyde Dehydrogenase Genotypes,. Cancer Epidemiology, Biomarkers &
Prevention , 1227.