Metabolic interactions of aldehyde dehydrogenase with therapeutic and toxic agents.

The specific physiological roles of ALDH have not been determined. In this overview, we have identified malondialdehyde as one potential endogenous toxic aldehyde that is oxidized by ALDH. Undoubtedly, there are other cytotoxic aldehydes which occur in several different tissues that are detoxified by this same system of enzymes. Intuitively, the role of aldehyde dehydrogenases in the detoxification of xenobiotic aldehydes should also receive additional consideration and attention. An interesting feature of specific studies described in this overview is that a single aldehydic substrate, like malondialdehyde, may be a substrate for one ALDH isozyme and a potent inhibitor of ALDH present in another cellular compartment. Assuming that the ALDH susceptible to this inhibition performs other important physiological or biochemical functions, a potentiating effect would occur. Thus, the efficient metabolism of potentially cytotoxic aldehydes may be a protective mechanism against a number of different organ system pathologies. Another striking feature of ALDH is its sensitivity to in vitro and in vivo inhibition by a number of chemically and pharmacologically diverse agents. This characteristic suggests that ALDH may be a target enzyme for inhibition by several therapeutically important drugs or their metabolites. As a result, the perturbation of ALDH by specific therapeutic agents suggests a potential role of this enzyme in a number of different drug-induced toxicities.