Chai X, Zhai Y, Napoli J L
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214, USA.
Gene. 1996 Mar 9;169(2):219-22. doi: 10.1016/0378-1119(95)00833-0.
The primary and rate-limiting step in retinoic acid (RA) biosynthesis requires the conversion of retinol into retinal. Previously, two genes encoding retinol dehydrogenases (RoDH), which recognize holo-cellular retinol-binding protein as substrate, had been cloned, expressed and identified as members of the short-chain dehydrogenase/reductase (SDR) gene family. This work reports the cloning of a cDNA encoding a third RoDH isozyme, RoDH(III). The deduced amino-acid sequence of RoDH(III) indicates 97.8% identity with RoDH(I) and 82.3% identity with RoDH(II). RNase protection assays revealed RoDH(III) mRNA expression only in rat liver, in contrast to RoDH(I) and RoDH(II), which had their mRNA expressed in rat liver, kidney, lung, testis and brain. These data extend the insight that a subfamily of SDR isozymes, tissue-distinctively expressed, catalyzes the first step in RA biogenesis.
维甲酸(RA)生物合成的主要限速步骤需要将视黄醇转化为视黄醛。此前,已克隆、表达了两个编码视黄醇脱氢酶(RoDH)的基因,它们将全细胞视黄醇结合蛋白识别为底物,并被鉴定为短链脱氢酶/还原酶(SDR)基因家族的成员。这项工作报道了编码第三种RoDH同工酶RoDH(III)的cDNA的克隆。RoDH(III)推导的氨基酸序列与RoDH(I)有97.8%的同一性,与RoDH(II)有82.3%的同一性。核糖核酸酶保护分析显示,RoDH(III)mRNA仅在大鼠肝脏中表达,与之形成对比的是,RoDH(I)和RoDH(II)的mRNA在大鼠肝脏、肾脏、肺、睾丸和大脑中均有表达。这些数据拓展了我们的认识,即一组组织特异性表达的SDR同工酶亚家族催化了RA生物合成的第一步。