Aldehyde dehydrogenase

Aldehyde dehydrogenases are a group of enzymes that catalyse the oxidation (dehydrogenation) of aldehydes. Multiple forms exist in mammals in the cytosol, mitochondria and endoplasmic reticulum. They have been classified as Class 1 (cytosolic), Class 2 (mitochondrial) and Class 3 (tumour and other isozymes). In all three classes constitutive and inducible forms exist.

The overall reaction catalysed by the aldehyde dehydrogenases is:

RCHO + NAD(P)+ + H2O ↔ RCOOH + NAD(P)H + H+

Aldehyde dehydrogenases have a broad substrate specificity. Oxidation of aldehydes is considered to be generally a detoxification reaction, removing the electrophilic products of alcohol oxidation.

For example, alcohol dehydrogenase oxidizes ethanol to acetaldehyde, responsible for some “hangover” symptoms, and acetaldehyde dehydrogenase detoxifies this to acetic acid. Similarly aldehyde dehydrogenase detoxifies acrolein, the hepatotoxic metabolite formed from allyl alcohol. However, in the case of 2-butoxyethanol, alcohol and aldehyde dehydrogenases sequentially catalyse the formation of the hematotoxic metabolite, 2-butoxyacetic acid.

Aldehyde dehydrogenases can also behave as esterases, hydrolyzing esters such as para-nitrophenyl acetate.

A deficiency in these enzymes or a polymorphism which renders the enzyme inactive results in alcohol intolerance. Consumption of alcohol results in allergy-like symptoms including nasal congestion and flushing. This is most common of East Asian decent, and about 50% of Chinese, Korean and Japanese are somewhat alcohol intolerant. These symptoms are sometimes referred to as ‘oriental flushing syndrome’ or 'asian flush'.

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