Biology of disease. Alcoholism and aldehydism: new biomedical concepts.

New results of biomedical research in alcoholism show great interindividual, as well as racial, variability with respect to metabolism of alcohol and its first oxidation product, acetaldehyde. Genetic factors play an important part. The enzymes of alcohol and aldehyde metabolism exhibit a genetically determined heterogeneity (isoenzymes and enzyme polymorphisms). This leads to a large variety of individually different enzyme phenotypes. Thus, the hypothesis is put forward that the individual and racial differences in alcohol metabolism are based on the genetically determined variability of the participating enzymes, alcohol dehydrogenase and aldehyde dehydrogenase. Alcohol metabolism and alcohol-induced disturbances of the intermediary metabolism are closely interrelated. Hence, genetic codetermination can also be expected in this regard. As a toxic intermediate of alcohol metabolism, acetaldehyde plays a central role. Three positive ranges of acetaldehyde levels can be defined: (a) the normal range, (b) the "acute aldehyde syndrome" with extremely high levels of acetaldehyde, (c) "chronic aldehydism" with slightly elevated acetaldehyde levels. In Orientals lacking the mitochondrial low Km aldehyde dehydrogenase, acetaldehyde accumulates and produces symptoms of intoxication. This acute aldehyde syndrome is highly aversive and, thus, prevents these individuals from drinking. The effect is similar to the consequences of the inhibition of aldehyde dehydrogenase with disulfiram, a commonly employed drug in the treatment of alcoholics. In alcoholics slightly elevated levels of blood acetaldehyde are observed. There are indications that this chronic aldehydism is not only the consequence of excessive drinking but may reflect a preexisting enzyme pattern that is genetically determined. Therefore, slightly elevated acetaldehyde concentrations could serve as a biologic marker for high risk drinking. Alcohol dehydrogenase is found in many organs and often in specialized cells within a particular tissue. A specific enzyme pattern in these cells could lead to elevated acetaldehyde concentrations, consequently inducing acetaldehyde-related damage. Such organs could represent direct targets even at low blood acetaldehyde levels.