Human Liver High Km Aldehyde Dehydrogenase (ALDH4): Properties and Structural Relationship to the Glutamic γ-Semialdehyde Dehydrogenase
In humans aldehyde dehydrogenase (ALDH) represents an important metabolic system for the detoxification of aliphatic and aromatic aldehydes. Moreover, ALDH exhibits genetic heterogeneity and the polymorphic forms seem to contribute to differences in acute and chronic outcome of excessive alcohol drinking. Human liver contains a number of ALDH enzyme forms (isozymes) which differ in their kinetic, electrophoretic and structural properties (Harada et al., 1980; Pietruszko et al., 1987; Agarwal et al., 1990). The hepatic ALDH1 (cytosolic) and ALDH2 (mitochondrial) isozymes have a very low Km for acetaldehyde, and are supposed to play a major role in the oxidation of toxic acetaldehyde produced from ethanol. In stomach a high Km isozyme (ALDH3) form is present which shows a very high Km for acetaldehyde and propionaldehyde but a relatively low Km for aromatic aldehydes such as 3-nitrobenz-aldehyde (Eckey et al., 1991). A tumor-associated ALDH form, detected in a human hepatocarcinoma (Agarwal et al., 1989), shares many physico-chemical properties with the constitutive form of human stomach. In addition, a cathodically migrating mitochondrial ALDH enzyme, hitherto designated as E4 or ALDH4, has been characterized in human liver (Forte-McRobbie and Pietruszko, 1986).
KeywordsExcessive Alcohol Drinking ALDH Isozyme Human Aldehyde Dehydrogenase Aldehyde Dehydrogenase Isozyme Carbonyl Metabolism
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