Kinetic properties of the human liver cytosolic aldehyde dehydrogenase for retinal isomers

Retinoic acid exerts pleiotropic effects by acting through two families of nuclear receptors, RAR and RXR. All-trans and 9-cis retinoic acid bind RARs, whereas 9-cis retinoic acid binds and activates only the RXRs. To understand the role of human liver cytosolic aldehyde dehydrogenase (ALDH1) in retinoic acid synthesis, we examined the ability of ALDH1 to catalyze the oxidation of the naturally occurring retinal isomers. ALDH1 catalyzed the oxidation of all-trans, 9-cis, and 13-cis retinal with equal efficiency. However, the affinity to all trans retinal (K-m = 2.2 mu M) was twofold higher than to 9-cis (K-m = 5.5 mu M) and 13-cis (K-m = 4.6 mu M) retinal. All trans retinol was a potent inhibitor of ALDH1 activity, and inhibited all-trans retinal oxidation uncompetitively. Comparison of the kinetic properties of ALDH1 for retinal isomers with those of previously reported rat kidney retinal dehydrogenase showed distinct differences, suggesting that ALDH1 may pray a different role in retinal metabolism in liver. BIOCHEM PHARMACOL 57;2:195-197, 1999. (C) 1998 Elsevier Science Inc.