VERTEBRATE CAROTENOID ISOMERASES

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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.