Bhat P V, Samaha H
CHUM Research Center, Department of Medicine, Université de Montréal, Quebec, Canada.
Biochem Pharmacol. 1999 Jan 15;57(2):195-7. doi: 10.1016/s0006-2952(98)00261-5.
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 ALDH 1 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 (Km = 2.2 microM) was twofold higher than to 9-cis (Km = 5.5 microM) and 13-cis (Km = 4.6 microM) 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 play a different role in retinal metabolism in liver.
视黄酸通过作用于两类核受体RAR和RXR发挥多效性作用。全反式视黄酸和9-顺式视黄酸可结合RAR，而9-顺式视黄酸仅结合并激活RXR。为了解人肝细胞质醛脱氢酶（ALDH1）在视黄酸合成中的作用，我们检测了ALDH1催化天然存在的视网膜异构体氧化的能力。ALDH1能以相同效率催化全反式、9-顺式和13-顺式视黄醛的氧化。然而，其对全反式视黄醛的亲和力（Km = 2.2 microM）比对9-顺式视黄醛（Km = 5.5 microM）和13-顺式视黄醛（Km = 4.6 microM）高两倍。全反式视黄醇是ALDH1活性的强效抑制剂，且以非竞争性方式抑制全反式视黄醛的氧化。将ALDH1对视网膜异构体的动力学特性与先前报道的大鼠肾脏视网膜脱氢酶的动力学特性进行比较，结果显示存在明显差异，这表明ALDH1在肝脏视网膜代谢中可能发挥不同作用。
