VERTEBRATE CAROTENOID ISOMERASES

描述（由申请人提供）：视网膜通过称为光转导的生物化学过程将进入我们眼睛的光转化为电信号。然后，这个信号被传递到大脑的视觉皮层，在那里发生视觉感知。视觉系统使我们能够在一生中不断地感知光线，因为它具有再生蛋白质和光敏发色团的能力。光敏发色团11-顺式-视黄醛衍生自维生素A。视觉中最令人困惑和长期存在的问题之一是负责生色团再生的异构化机制。答案可能在于对植物类维生素A加工酶的研究。植物和光合细菌是除了动物之外唯一能够制造类胡萝卜素的生物。植物中参与类胡萝卜素代谢的一些酶与具有相同功能的脊椎动物蛋白有关。利用植物酶和脊椎动物基因组的序列分析，发现了另外的类维生素A加工酶，包括两个来自高等脊椎动物的类胡萝卜素异构酶样基因。目前正在研究这些基因在不同组织和细胞类型中的表达。为了进一步分析这些酶，建议在这里研究新发现的脊椎动物酶的生化测定，旨在阐明其在脊椎动物类维生素A代谢中的作用。此外，受遗传性失明影响的患者将接受这些基因突变的筛查。最后，将使用转基因动物模型研究这些酶对类维生素A加工的贡献，从而研究其对视觉的贡献。

DESCRIPTION (provided by applicant): The retina converts light entering our eyes into an electrical signal through a biochemical process called phototransduction. This signal is then relayed to the visual cortex of the brain, where visual perception occurs. The visual system allows us to continually perceive light throughout our lives because it has the ability to regenerate proteins and the light-sensitive chromophore. The light sensitive chromophore, 11-cis-retinal, is derived from vitamin A. One of the most puzzling and longstanding problems in vision is the isomerization mechanism responsible for chromophore regeneration. The answer may lie in the study of plant retinoid processing enzymes. Plants and photosynthetic bacteria are the only organisms other than animals capable of making carotenoids. Some of the enzymes involved in carotenoid metabolism in plants are related to vertebrate proteins with the same function. Using sequence analysis of plant enzymes and vertebrate genomes, additional retinoid processing enzymes were discovered, including two carotenoid isomerase-like genes from higher vertebrates. The expression of these genes in different tissues and cell types is currently under investigation. To further the analysis of these enzymes, it is proposed here to study the newly discovered vertebrate enzymes in biochemical assays designed to elucidate their role in vertebrate retinoid metabolism. In addition, patients affected by inherited forms of blindness will be screened for mutations in these genes. Lastly, the contribution of these enzymes to retinoid processing and, hence, to vision will be studied using transgenic animal models.