Aldehyde dehydrogenase genetic deficiency

Some populations, most notably East Asians, exhibit an unusual response after drinking ethanol. The symptoms include facial flushing, vasodilation, and tachycardia. These individuals apparently have a genetic deficiency of the enzyme aldehyde dehydrogenase, which leads to an accumulation of acetaldehyde even after they drink relatively small amounts of ethanol. If drugs such as metronidazole, griseofulvin, quinacrine, the hypoglycemic sulfonylureas, phenothiazines, and phenylbutazone are coadministered with ethanol, a similar accumulation of acetaldehyde may occur. 

The corresponding open-chain aldehyde, formed by hydrolysis, can be oxidized back to glutamate by pyrroline 5-carboxylate dehydrogenase. 145a 147 Lack of this enzyme is associated with the human genetic deficiency causing hyperprolinemia.147-1483... 

Some people, primarily of Asian descent, have a genetic deficiency in the activity of the mitochondrial form of aldehyde dehydrogenase. When these individuals drink alcohol, they develop high blood acetaldehyde concentrations and experience a flushing reaction similar to that seen with the combination of disulfiram and ethanol. 

Intolerance. Inter-ethnic variation in tolerance to alcohol is well recognised, for Asian persons, particularly Japanese, develop flushing, headache and nausea after what are, by Caucasian standards, small amounts of the substance. Genetic deficiency of aldehyde dehydrogenase with slow metabolism of (toxic) acetaldehyde may explain these features. 

The enzymes are widely distributed in microorganisms, plants, and animals. " Three Mo-MPT enzymes have been found in mammals (1) xanthine dehydrogenase see Dehydrogenase) has many, varied roles in purine catabolism, drug metabolism, and oxidative stress response, (2) aldehyde oxidase is important in drug metabolism and the synthesis of retinoic acid from retinal, and (3) sulfite oxidase plays a cmcial role in the detoxification of sulfite produced in the degradation of cysteine and methionine. Genetic Mo-MPT deficiency in... 

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