More details about alcohol flush reaction

There are many theories that try to explain why there is a defective gene spread extensively in some populations, yet we do not have an exact answer for the time being. However, scientists agree when saying that a mutation occurred quite late in human history. One of the theories states that there was less of a probability of alcoholism in people, and that is why they had more descendants. This reasoning does not explain why the defective gene is so frequent only in Asia.

About metabolism of alcohol

Alcohol in alcoholic beverages is, chemically speaking, ethanol. Ethanol enters from the digestive system into the blood and has numerous toxic effects. As a result cells have mechanisms, which degrade ethanol into acetic acid, carbon dioxide and water. The first step in the metabolism of alcohol is the transformation of ethanol to acetaldehyde. This compound is even more toxic than ethanol itself and the negative consequences of drinking alcohol originate mostly from the toxic effects of this compound. It is thus important for cells to have mechanisms that can quickly transform it into acetic acid. Two enzymes perform this function. The first one is ALDH1 (acetaldehyde dehydrogenises 1) and the second one is ALDH2 (acetaldehyde dehydrogenises 2). In the third step the acetic acid transforms into acetyl-CoA, which becomes part of the further metabolic processes in the cell.

Scientists have discovered that a defect in the enzyme ALDH2 is responsible for the over sensitivity towards alcohol. The improper functioning of this enzyme causes acetaldehyde not to be removed from cells fast enough. The majority of Asians, who have a less active form of the enzyme, have guanine (G) switched in the same spot with adenine (A) in the ALDH2 gene. As a result there is a switch of amino acids, which disables functioning.

ALDH2 gene

Each human has two copies of each gene, which they have inherited from their parents. It is characteristic for people who have both defective gene copies not to consume alcoholic beverages as it has an ill effect on their state of health. This is understandable as the level of acetaldehyde has increased greatly. The other possibility is that only one copy of the gene is defective. People with only one working copy of ALDH2 also have problems tolerating alcohol. The causes for this are the units of the enzyme ALDH2, which couple into complexes. Four functional units need to be coupled in a complex in order for the enzyme to function properly. Probability calculations estimate that in the end there is only six percent of such complexes active, with one defective ALDH2 gene variant. And this is not enough for a normal metabolism of alcohol.

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