Substituent effects during the rat liver aldehyde dehydrogenase catalyzed oxidation of aromatic aldehydes.

The influence of the steric hindrance of halogen substituents was investigated in vitro by measuring the activity of yeast aldehyde dehydrogenase (aldehyde: NAD(P)+ oxidoreductase, EC 1.2.1.5) and of aldehyde dehydrogenases in subcellular rat liver fractions with a series of ortho- and para-halo-substituted benzaldehydes as substrates. Upon an increase in the size of the halogen substituent (F, Cl, Br), the reactivity of yeast aldehyde dehydrogenase to ortho-substituted benzaldehydes decreased drastically. The same phenomenon was observed with the unspecific aldehyde dehydrogenases in three rat liver fractions; cytoplasm, mitochondria and microsomes. The corresponding para-halobenzaldehydes (F, Cl, Br, I) did not reveal large differences in reactivity to the various rat liver aldehyde dehydrogenases. The aldehyde dehydrogenases in the rat liver microsomal fraction exhibited most clearly the regiospecificity. Enzymatic oxidation of 4-bromobenzaldehyde was more than 30-times faster then the ortho-isomer. The findings in this investigation confirm the suggestion that the steric hindrance of bulky ortho-substituents of benzaldehydes account for the slowing down of the aldehyde dehydrogenase-catalyzed oxidation of benzaldehydes to corresponding benzoic acids. The enzymatic oxidation of microsomal aldehyde dehydrogenase is strongly influenced by steric effects of benzaldehydes, bearing a halogen in ortho-position. We think that the microsomal aldehyde dehydrogenase might be the principal enzyme responsible for oxidation of halobenzaldehydes in rat liver.