VERTEBRATE CAROTENOID ISOMERASES

脊椎动物类胡萝卜素异构酶

• 批准号: 6879494
• 负责人: KRZYSZTOF PALCZEWSKI
• 金额: $ 10.11万
• 依托单位: UNIVERSITY OF WASHINGTON
• 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 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6879494
• 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）：视网膜通过称为光导的生化过程将进入我们眼睛的光转换为电信号。然后这个信号被传递到大脑的视觉皮层，在那里产生视觉感知。视觉系统使我们能够在一生中不断地感知光，因为它有能力再生蛋白质和光敏感的发色团。光敏感的发色团，11-顺式视网膜，来源于维生素a。其中一个最令人困惑和长期存在的问题是负责发色团再生的异构化机制。答案可能就在对植物类维甲酸加工酶的研究中。植物和光合细菌是除动物外唯一能够制造类胡萝卜素的生物。一些参与植物类胡萝卜素代谢的酶与具有相同功能的脊椎动物蛋白质有关。利用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个类胡萝卜素异构酶样基因。这些基因在不同组织和细胞类型中的表达目前正在研究中。为了进一步分析这些酶，本文建议对生物化学分析中新发现的脊椎动物酶进行研究，以阐明它们在脊椎动物类视黄醇代谢中的作用。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，这些酶对类视黄醇加工的贡献，因此，视觉将使用转基因动物模型进行研究。