Alcohol addiction: Why are some people are alcoholic than others?





Alcohol abuse  is one of the biggest problems affecting people in the community. Its effects are evidenced in our families, workplaces, public, etc.  Alcohol has enslaved and reduced many people to undesirable conditions. Why are some people more addicted to alcohol than others? This article addresses the biochemical reasons to help you understand what you may become if you start drinking alcohol.

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The isozymes and genetics determine whether one will be an alcoholic or not. What are isozymes? Isozymes are enzymes that catalyze the same reaction though they migrate differently on the electrophoresis . Electrophoresis is a technique used to separate charged particles based on their charges and weight. The mechanism for the formation of the isozymes encompasses the arrangement of the subunits arising from two genetic loci (ADH 1 and ALDH 2) in various arrangements to form an active polymeric enzyme. The Alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) catalyze the oxidation of ethanol and acetaldehyde in the presence of oxidized biofactor (NAD+) respectively. 

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Dehydrogenase System of Alcohol (Ethanol) in the Body
CH3-CH2OH + NAD+ = CH3-COH + NADH
Ethanol                             Acetaldehyde
Enzyme: Alcohol Dehydrogenase (ADH)

CH3-COH + NAD+ = CH3-COOH + NADH
Acetaldehyde               Acetate
Enzyme: Acetaldehyde dehydrogenase

The molecule of Alcohol dehydrogenase is a dimer. Three genetic loci(ADH 1, ADH 1B and ADH 1C) encode its alpha-, Beta- and gamma- constituents.  Genetic locus ADH 1A has little effects on the oxidation of the ethanol, therefore, this article focuses on the ADH 1B, ADH 1C and the locus ALDH 2.
 
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ADH 1B locus
This gene is polymorphic and consists of three alleles encoding the Beta-1, Beta-2 and Beta-3 subunits of ADH enzyme. The three subunits of the enzyme differ from each other according to the amino acid substitution. Arg, His47, and Cys369 proteins are substituted in Beta-1, Beta-2, and Beta-3 subunits respectively. The amino acid substitution on the enzyme subunits brings significant change in the kinetic characteristics of the ADH enzyme. The rate of ethanol oxidation is greater in the individuals with Beta-3Beta-3, followed by Beta-2Beta-2 and finally Beta-1Beta-1 isozymes.

ADH 1C locus
ADH 1C has two alleles that encode gamma-1 and gamma-2 subunits of the Alcohol dehydrogenase enzyme. The gamma-1 gamma-1 isozyme generates acetaldehyde faster than the gamma-2gamma-2  isozyme.

ALDH 2 locus
The Acetaldehyde Dehydrogenase  is a tetramer. Three polymorphic genetic loci encode its constituents. According to studies, the family of ALDH isozymes is classified into three classes based on their subcellular locations, catalytic, and structural properties. However, only two categories (1 and 2) involve in the oxidation of acetaldehyde. ALDH 2*1 is located in the mitochondrion and has a high affinity for acetaldehyde, and contributes to the greater quantities of oxidation of acetaldehyde in the human liver.  ALDH 2*2 has little affinity for acetaldehyde, hence, it oxidizes acetaldehyde to acetate at a low rate.  

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The rate of oxidation of ethanol and elimination of acetaldehyde from the body determine whether someone will be alcohol addict or not. When there is a high rate of ethanol oxidation and lower acetaldehyde oxidation, the person will not be alcoholic. On the other hand, if the rate of oxidation of both ethanol and acetaldehyde are high, the person will be addicted to alcohol. One will not be alcoholic if both rates are low. The primary determinant factor is the amount of acetaldehyde in the body; if it is high, then one will dislike alcohol and will not drink more alcohol. People response differently according to the types of isozymes and the genetics (ADH 1 and ALDH 2) they have in their bodies. Individuals with isozymes Beta-3 Beta-3, Beta-1Beta-1, and ALDH 2*1 will probably be alcoholic as opposed to people with Beta-2 Beta-2, gamma-1 gamma-1, and ALDH 2*2 isozymes. 
 
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