Inactive/Ineffective acetaldehyde dehydrogenase syndrome
(inactive/ineffective ethanal dehydrogenase)
Website dedicated to the inactive/ineffective acetaldehyde dehydrogenase syndrome
WORK IN PROGRESS
Draft Version 1.2.3 (September 2010)
Update: For a very good, easy to understand introduction, we suggest to read:
Acetaldehyde - A Common and Potent Neurotoxin by Herbert Sprince and John Cleary
For more recent insights and more details have a look at:
Putative Role of brain Acetaldehyde... by Xin-sheng Deng and Richard A. Deitrich
We will try to include insights and quotes of both articles into our summary on acetaldehyde within the next few months.:
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Introduction
Acetaldehyde, or Ethanal (UIPAC), CH3CHO
Toxicity comparable to formaldehyde, carcinogenic
Note: Acetaldehyde is more toxic than alcohol itself, hangover symptoms are related to acetaldehyde.
In it's pure form Acetaldehyde is a flammable liquid with a fruity smell.
Natural occurrence: primary source is alcohol, secondary sources are tobacco smoke, coffee,
certain fruits and plants, intestinal ethanol fermentation/ – in the case of yeast syndrome (Candida albicans): sugar fermentation (cure: Bifidus)–, synthetic resins, synthetic dyestuffs (for formaldehyde detoxification acetaldehyde dehydrogenase is required as well!)and more... Acetaldehyde is also an air pollutant resulting from combustion, such as automotive exhaust.
Acetaldehyde dehydrogenases are dehydrogenase enzymes
which catalyze the conversion of acetaldehyde into ?acetic acid? acetate?
The oxidation of acetaldehyde to ?acetic acid? acetate?can be summarized as follows:
CH3CHO + NAD+ + CoA → acetyl-CoA + NADH + H+
(source wikipedia corrected, wikipedia wrongly indicates acetate instead of acetic acid)
Remarks 9/2010: We are looking in to this again, and while a former high school teacher insisted it would be wrong to indicate it is acetate, most articels point out it is indeed acetate.
Ethanol / Alcohol dehydrogenase
In the liver, the enzyme alcohol dehydrogenase converts ethanol into acetaldehyde, which is then further converted into harmless acetic acid by acetaldehyde dehydrogenase.
(The last steps of alcoholic fermentation in bacteria, plants and yeast involve the conversion of pyruvate into acetaldehyde by the enzyme pyruvate decarboxylase, followed by the conversion of acetaldehyde into ethanol.)
Accumulation of Acetaldehyde
Inactive/ineffective acetaldehyde dehydrogenase can lead to severe accumulation of acetaldehyde
and persisting levels of acetaldehyde (up to several days),
which obviously is very unhealthy and can lead to irreversible damage.
We also observed build up of unhealthy acetaldehyde levels in cases of exposure
to even minor amounts of alcohol or secondary sources like tobacco smoke, coffee, etc. (>Image 1)
Different kinetic properties of ADHL-Variations
Visualization: Metabolism Timeframe (>Image 2)
Comparison of Acetaldehyde Levels
with active to inactive acetaldehyde dehydrogenase
Mitochondrial ADHL, ect.
Prevalence of inactive/ineffective acetaldehyde dehydrogenase
....approx. 50% of Asian Population, approx. 10% of predominantely Caucasian inheritance...
Polymorphisms: ALDH2, heterozygous <-> homozygous
Discussion Part I:
Clarification and Distinction, Disambiguation
The Asian Flush Reaction is mainly related to another cause: a highly rapid version of the enzyme alcohol dehydrogenase (ethanol dehydrogenase): The rapid accumulation of acetaldehyde causes the reaction observed as "Flush" due to exceptionally high levels of acetaldehyde: symptoms include skin turning red immediately after alcohol intake et al.
Combined with a slow metabolism of acetaldehyde through ineffective/inactive acetaldehyde dehydrogenase
a high level of acetaldehyde may remain over a period of several days.
Further Remarks and Discussion Part II:
Correction of Presentation in Popular Assessments (1/11/09)
Some popular sources [1] relate the Flush Reaction mainly to ineffective acetaldehyde dehydrogenase, even though the flush reaction is primarily related to the rapidity of alcohol dehydrogenase.
We must distinguish:
A. rapid accumulation of acetaldehyde caused by highly effective alcohol dehydrogenase
B. persistence of high levels of acetaldehyde due to ineffective/inactive acetaldehyde dehydrogenase
C. further accumulation of acetaldehyde after a following event of alcohol intake (or other sources) adding to a persistent ground level of acetaldehyde due to ineffective/inactive acetaldehyde dehydrogenase.
Inactive/ineffective acetaldehyde dehydrogenase and Asian Flush Reaction must be discussed as two separate phenomena.
In some cases affected persons only suffered from inactive/ineffective acetaldehyde dehydrogenase, but had no visible Flush Reaction. In this case the accumulation of acetaldehyde was severe, but often wasn't detected by medical professionals, because they expected the Flush Reaction to be the indicator for inactive/ineffective acetaldehyde dehydrogenase, which of course it is not. In these cases acetaldehyde intoxication was wrongly ruled out as the reason for discomfort and hangover symptoms such as depression.
Inaccurate understanding and wrong assumptions about the metabolism of acetaldehyde seem to be wide spread, also among medical professionals.
We highly recommend that medical schools dedicate more time of the academic curriculum to this issue.
Discussion Part III
Acetaldehyde as an air pollutant resulting from automotive exhaust
"Acetaldehyde occurs in vehicle exhaust at levels of
1.4-8.8 mg/m3 in gasoline exhaust, about 5.8 mg/m3 in diesel
exhaust (Verschueren, 1983), and 51.6% acetaldehyde/ n-hexane GC peak
area ratio in exhaust gas oxygenates (Hugues & Hum, 1960)." [2]
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[1] Following article needs to be more precise: http://en.wikipedia.org/wiki/Asian_flush)
Good Source:
[2] INTERNATIONAL PROGRAM ON CHEMICAL SAFETY
http://www.inchem.org/documents/ehc/ehc/ehc167.htm
WIKIPEDIA
http://en.wikipedia.org/wiki/Acetaldehyde_dehydrogenase
http://en.wikipedia.org/wiki/Acetaldehyde
Genetic Polymorphism's of Alcohol and Aldehyde Dehydrogenases and Risk for Esophageal and Head and Neck Cancers
http://jjco.oxfordjournals.org/cgi/content/abstract/33/3/111
Draft Images
1. Asian Flush (highly effective alcohol dehydrogenase) vs. Slow (Normal) build up of acetaldehyde level
2. 24 hours: 4 diagrams of acetaldehyde build up / decline in comparison
3. Accumulation/Build up of Acetaldehyde levels with inactive/ineffective acetal dehydrogenase featuring several minor events on timeline.
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