Interaction of human aldehyde dehydrogenase with aromatic substrates and ligands.
The substrate benzaldehyde (but not propionaldehyde) could elute aldehyde dehydrogenase from a p-hydroxyacetophenone-affinity column, and inhibit the esterase activity (K(i)=47 microM), indicating that this simple aromatic aldehyde binds to the free enzyme and possibly in the substrate-binding site. Thus, the kinetic mechanism for aldehyde dehydrogenase might be dependent upon which aldehyde is used in the reaction. Chloramphenicol which also elutes the enzyme from the affinity column, shows a discriminatory effect by inhibiting the ALDH1 oxidation of benzaldehyde and activating that of propionaldehyde while showing no effect when assayed with hexanal or cyclohexane-carboxaldehyde. Chloramphenicol is an uncompetitive inhibitor against NAD when benzaldehyde is the substrate. We propose that this drug might interact with both the benzaldehyde and NAD binding sites.
Allali-Hassani
A
A
Biochemistry Department, Biochemistry Building 1153, Purdue University, 47907-1153, West Lafayette, IN, USA.
Weiner
H
H
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000447:Aldehydes / Q000378:metabolism; D001547:Benzaldehydes / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D002701:Chloramphenicol / Q000494:pharmacology; D002846:Chromatography, Affinity; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D009243:NAD / Q000378:metabolism; D050697:Retinal Dehydrogenase; D013379:Substrate Specificity
D000447:Aldehydes; D001547:Benzaldehydes; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008024:Ligands; D009243:NAD; D002701:Chloramphenicol; C005556:propionaldehyde; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; C032175:benzaldehyde