Human aldehyde dehydrogenase: catalytic activity in oriental liver

Area of Science:

• Biochemistry
• Human Genetics
• Enzymology

Background:

• A "null" mutation in mitochondrial aldehyde dehydrogenase (ALDH2) E2 isozyme was previously suggested in alcohol-sensitive Oriental populations.
• This proposed "null" mutation was thought to explain alcohol sensitivity in certain ethnic groups.

Purpose of the Study:

• To investigate the catalytic activity and biochemical properties of the human aldehyde dehydrogenase E2 isozyme in Oriental individuals.
• To determine if the Oriental E2 isozyme is indeed a catalytically inactive "null" mutant or if it possesses enzymatic activity.

Main Methods:

• Purification of the mitochondrial E2 isozyme of human aldehyde dehydrogenase from Oriental individuals.
• Biochemical characterization of the purified Oriental E2 isozyme, including assessment of catalytic activity.
• Comparison of kinetic parameters (e.g., maximal velocity) and physicochemical properties (e.g., isoelectric point) with the Caucasian E2 isozyme.

Main Results:

• The Oriental E2 isozyme, contrary to previous suggestions, is catalytically active.
• The Oriental and Caucasian E2 isozymes are largely identical, with differences noted in maximal velocity and isoelectric point.
• The observed alterations in the Oriental E2 isozyme are not located within the active site of the enzyme.

Conclusions:

• The Oriental aldehyde dehydrogenase E2 isozyme is not a "null" mutant but is catalytically active.
• The differences observed between Oriental and Caucasian E2 isozymes do not involve the active site, suggesting a different type of mutation.
• This finding challenges the previous understanding of alcohol sensitivity in Oriental populations related to a non-functional ALDH2 enzyme.