VERTEBRATE CAROTENOID ISOMERASES

脊椎动物类胡萝卜素异构酶

• 批准号: 7180685
• 负责人: KRZYSZTOF PALCZEWSKI
• 金额: $ 5.05万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7180685
• 关键词: blindness; carotenoids; enzyme activity; gene expression; gene mutation; gene targeting; genetically modified animals; high performance liquid chromatography; immunocytochemistry; in situ hybridization; isomerase; laboratory mouse; protein protein interaction; protein structure function; retinoids; vision; vitamin metabolism

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.

描述（由申请人提供）：视网膜通过称为光转导的生化过程将进入我们眼睛的光转换为电信号。然后该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感知光，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-顺式视黄醛源自维生素 A。视觉中最令人费解且长期存在的问题之一是负责发色团再生的异构化机制。答案可能在于对植物类视黄醇加工酶的研究。植物和光合细菌是除动物之外唯一能够制造类胡萝卜素的生物体。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。通过对植物酶和脊椎动物基因组的序列分析，发现了其他类视黄醇加工酶，包括来自高等脊椎动物的两种类胡萝卜素异构酶基因。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，本文建议在生化测定中研究新发现的脊椎动物酶，旨在阐明它们在脊椎动物类维生素A代谢中的作用。此外，还将对受遗传性失明影响的患者进行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加工以及视觉的贡献。