Human Umami Taste: Genetics of Psychophysical Traits

描述（由申请人提供）：氨基酸（尤其是谷氨酸）的鲜味和甜味是两种令人食欲的味觉品质，它们对我们对蛋白质和碳水化合物（能量）常量营养素的健康吸引力至关重要。食欲蛋白味觉系统的进化压力可能是我们的营养需求：获得膳食蛋白质来源是生存所必需的，而营养不良（膳食蛋白质缺乏）是发展中国家儿童死亡的主要原因之一。尽管在饮食选择中很重要，但人类鲜味仍然是五种味道品质中最不为人所知的味道之一，其遗传和分子决定因素在很大程度上仍然未知。在味觉受体细胞中发现的三类谷氨酸受体与氨基酸和核糖核苷酸的细胞信号传导有关：(i) TAS1Rs, （ii）代谢嗜性glurs和（iii）离子嗜性nmda受体。然而，它们各自在人类鲜味感知中的作用尚不清楚。这项工作的长期目标是阐明人类感觉“鲜味”的遗传和分子机制。该项目的目标是阐明这三种受体类别的作用，确定可能与人类鲜味味觉感知有关的其他基因，并对与鲜味表型相关的变异受体进行功能测试。本建议的具体目的是：

DESCRIPTION (provided by applicant): The umami taste of amino acids (especially glutamate) and sweetness are the two appetitive taste qualities that are critical for our healthy attraction to protein and carbohydrate (energy) macronutrients. The likely evolutionary pressure for an appetitive protein taste system is our nutritional need: access to sources of dietary protein is essential for survival and kwashiorkor (dietary protein deficiency) is one of the leading causes of death in children in developing countries. Despite its importance in dietary selection, human umami taste remains one of the most poorly understood of the five taste qualities and its genetic and molecular determinants remain largely unknown. Three classes of glutamate receptors found within taste receptor cells have been associated with cell signaling in response to amino acids and ribonucleotides: (i) TAS1Rs, (ii) metabotropic-GluRs, and (iii) ionotropic-NMDA receptors. However, their respective roles in human umami taste perception are not known. The long term goal of the proposed work is to elucidate genetic and molecular mechanisms that are responsible for the human sensation of `umami' taste. The objectives of the proposed project are to clarify the roles of these three receptor classes, to identify other genes that may be involved with human umami taste perception, and to functionally test variant receptors associated with umami phenotypes. The specific Aims of this Proposal are: I. Identify variant genes and/or genome-wide loci associated with umami blindness. II. Characterize any umami perceptual phenotypes related to glutamate receptor SNPs. III. Define variant glutamate receptor stimulus-response functions in expression assays.PROJECT NARRATIVE This proposal will contribute to human health by identifying genes associated with human protein/amino acid taste (umami), which will subsequently guide nutritional intervention in protein malnourished people. Taste is significantly linked to nutrition, since our decision to accept or reject foods is ultimately based on our evaluation of food tastes. Hence, people who lose their sense of taste, such as radiotherapy patients, suffer nutrionally. Frequently, children in developing nations prefer foods with high levels of sugar, when available, over other food types. Too little protein in the diet (Kwashiorkor) is associated with one in every two children's deaths in the developing world. Since children with protein malnutrition prefer foods that have added free amino acids in experimental settings, a better understanding of amino acid taste mechanisms could guide the engineering of more appetitive foods that could help alleviate their malnutrition. Despite its importance in dietary selection, human umami taste remains one of the most poorly understood of the five taste qualities and its genetic and molecular determinants remain largely unknown. We will characterize how genes of candidate umami taste receptors and other genetic loci affect perceptual attributes of human amino acid taste through interdisciplinary studies that combine human perception, genetics, and molecular receptor functions.