Posted by Larry Hoover on April 12, 2009, at 9:54:42
In reply to Re: depression and alcohol--is my pdoc right? » garnet71, posted by Deneb on April 11, 2009, at 1:33:08
> For readers who like biology stuff, this enzyme is known as the low-Km aldehyde dehydrogenase isoenzyme, or in short, ADH. The absence of this enzyme is the culprit for your flushed cheeks and feelings of sickness in response to alcohol use. Without this enzyme, the byproduct of alcohol (the toxic aldehyde dehydrogenase) cannot be removed from the bloodstream nearly as well as it is in people who do have the enzyme. The aldehyde accumulates in a person's system as a result because it cannot be broken down as quickly.
Just a little correction to the quoted text, and some background....
"Without this enzyme, the byproduct of alcohol (the toxic aldehyde dehydrogenase)..."Where it says toxic aldehyde dehydrogenase, it is incorrect. Any reference to dehydrogenase refers to the enzyme, and that is not toxic. The substrate for the enzyme, aldehyde, is toxic.
The aldehyde intermediate of the two-step oxidation of ethanol to ethanoic acid (acetic acid, or common vinegar) is called ethanal (modern name) or acetaldehyde (historic name).
Many people of Asian decent have an inefficient enzyme for processing ethanal. Very few people have zero activity. After this enzyme inefficiency was identified as the cause of the unpleasant response to ethanol, an inhibitor of this enzyme was developed to treat alcoholism, by making it very unpleasant. That drug (disulfiram) is marketed as Antabuse. People on this drug, which causes zero activity at this enzyme, get violently ill from even trivial exposure to ethanol.
The genetic defect that is common in Asian people is NOT the lack of the enzyme, but that the structure of their enzyme has a single point mutation. One amino acid is the wrong one. The co-factor NADH does not bind efficiently to the enzyme because of this defect, and the rate of the enzyme is correspondingly reduced to about 8% of that of people without the defect.
It has been theorized that supplemental niacinamide (precursor to NADH), or supplemental NADH (Enada is one brand), might reduce the adverse effects caused by low co-factor binding efficiency. For biochemist geeks, this enzyme is one of the rare ones with zeroth order kinetics. Its rate is unaffected by alcohol concentration, but instead only by its ability to exist in activated form, i.e. bound with its co-factor.
Lar
poster:Larry Hoover
thread:889629
URL: http://www.dr-bob.org/babble/20090408/msgs/890096.html