Yan W, Jang G F, Haeseleer F, Esumi N, Chang J, Kerrigan M, Campochiaro M, Campochiaro P, Palczewski K, Zack D J
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
Genomics. 2001 Mar 1;72(2):193-202. doi: 10.1006/geno.2000.6476.
Retinoids play a critical role in vision, as well as in development and cellular differentiation. beta,beta-Carotene-15,15'-dioxygenase (Bcdo), the enzyme that catalyzes the oxidative cleavage of beta,beta-carotene into two retinal molecules, plays an important role in retinoid synthesis. We report here the first cloning of a mammalian Bcdo. Human BCDO encodes a protein of 547 amino acid residues that demonstrates 68% identity with chicken Bcdo. It is expressed highly in the retinal pigment epithelium (RPE) and also in kidney, intestine, liver, brain, stomach, and testis. The gene spans approximately 20 kb, is composed of 11 exons and 10 introns, and maps to chromosome 16q21-q23. A mouse orthologue was also identified, and its predicted amino acid sequence is 83% identical with human BCDO. Biochemical analysis of baculovirus expressed human BCDO demonstrates the predicted beta,beta-carotene-15,15'-dioxygenase activity. The expression pattern of BCDO suggests that it may provide a local supplement to the retinoids available to photoreceptors, as well as a supplement to the retinoid pools utilized elsewhere in the body. In addition, the finding that many of the enzymes involved in retinoid metabolism are mutated in retinal degenerations suggests that BCDO may also be a candidate gene for retinal degenerative disease.
视黄醛在视觉、发育和细胞分化过程中发挥着关键作用。β,β-胡萝卜素-15,15'-双加氧酶（Bcdo），即催化β,β-胡萝卜素氧化裂解为两个视黄醛分子的酶，在视黄醛合成中起着重要作用。我们在此报道了首个哺乳动物Bcdo的克隆。人BCDO编码一个由547个氨基酸残基组成的蛋白质，与鸡的Bcdo有68%的同源性。它在视网膜色素上皮（RPE）中高表达，在肾脏、肠道、肝脏、大脑、胃和睾丸中也有表达。该基因跨度约20kb，由11个外显子和10个内含子组成，定位于16号染色体q21-q23区域。还鉴定出了小鼠的同源物，其预测的氨基酸序列与人类BCDO有83%的同源性。对杆状病毒表达的人BCDO进行生化分析，证实了其具有预测的β,β-胡萝卜素-15,15'-双加氧酶活性。BCDO的表达模式表明，它可能为光感受器提供局部视黄醛补充，同时也为身体其他部位利用的视黄醛库提供补充。此外，许多参与视黄醛代谢的酶在视网膜变性中发生突变这一发现表明，BCDO也可能是视网膜退行性疾病的候选基因。
