Those of you who have been in any sort of alcohol-related setting have probably seen at least one of your fellow students, most likely of Asian descent, taking on a fairly red complexion after as little as one drink. Maybe you are one of those drinkers who turns that rather embarrassing color and experiences a general feeling of warmth in the skin around their body, followed by some level of exhaustion and other unpleasant sensations such as an elevated heartrate.
This condition, formally called Alcohol Flush Reaction (slang terms include Asian Red or Asian Glow for its occurrence among Asians), arises from a defect in a particular copy of an enzyme called acetaldehyde dehydrogenase. The enzyme is responsible for an intermediate step in the metabolism of alcohol within the liver, breaking down acetaldehyde into acetic acid after another enzyme converts alcohol into acetaldehyde.
Cytosolic acetaldehyde dehydrogenase enzymes, typically found moving about the insides of liver cells, are primarily responsible for the breakdown of acetaldehyde, so a defect in the cytosolic acetaladehyde dehydrogenases can cause a buildup of acetaldehyde. That accumulation of acetaldehyde throughout the body leads to the flushing in the skin of the head and neck, with some individuals experiencing skin flushing all over the body. There is still another version of the enzyme that the body relies on, found in the mitochondria of liver cells, which will eventually break down the acetaldehyde. However, it works at a much lower rate.
The difference in the speeds of the enzymes arises from their Michaelis constants (Km), an important biochemical property of enzymes, which is higher in the cytosolic acetaldehyde dehydrogenase than it is in its mitochondrial counterpart. According to Chris Berndsen, a postdoctoral fellow in the Department of Biophysics and Biophysical Chemistry at the Hopkins School of Medicine, the Michaelis constant relates how fast an enzyme operates based on the concentration of the chemical it breaks down.
"The Michaelis constant in its simplest form is the amount of the substrate that you would need to reach one half of the fastest activity that the enzyme can have," he said. "In terms of impacting the enzyme, the Km really is a way for nature to tune the activity of the enzyme."
With a lower Km, the cytosolic enzyme works through the acetaldehyde faster than its mitochondrial counterpart; for enzymes in general, the Km alone does not indicate how fast the enzyme works.
"It's hard to correlate the raw activity to a higher Km because the maximal rate is a separate constant from the Km," Berndsen said. "If you have a very low Km, meaning that the metabolites are binding to the enzyme more efficiently and staying on the enzyme more efficiently, and a very slow rate, the enzyme will always be essentially going at that slow rate. The same thing works with a higher rate, but the relationship between the ability of the enzyme to turn over the metabolite, to bind it are, in the simplest form, largely separate."
This slowed ability to break down acetaldehyde may seem like an overall detriment, making the consumption of alcohol a fairly unpleasant experience. Its only benefit is to discourage irresponsible partying, and along those lines the trait does decrease the risk of alcoholism in affected individuals. Still though, what originally led to the heightened frequency of Alcohol Flush Reaction among Asian populations?
According to research from the Chinese Academy of Science published last year, the roots of Alcohol Flush Reaction go back to the time rice cultivation began. To be more specific, rice cultivation also involved the development of fermentation, resulting in alcohol and its disinfectant, analgesic and mental effects that we know very well. Consequently, the inheritable trait for Alcohol Flush Reaction mitigated overconsumption of alcohol and affected behaviors and mortality risks. The research group connected their molecular dating of a particular mutation back 7000 to 10,000 years ago with archaeological sites of the origins of rice cultivation.
In essence, what seems today to be a condition that is very unfavorable for certain social settings is as old as alcohol production itself in East Asia where it had a significant health benefit.
