Human Umami Taste: Genetics of Psychophysical Traits

描述（由申请人提供）：氨基酸（特别是谷氨酸盐）的鲜味和甜味是两种食欲味道品质，对于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。食欲蛋白质味觉系统可能的进化压力是我们的营养需求：获得膳食蛋白质来源对生存至关重要，而营养蛋白质缺乏症（Kwashiorkor）是发展中国家儿童死亡的主要原因之一。尽管它在饮食选择中的重要性，但人类的鲜味仍然是五种味觉品质中了解最少的一种，其遗传和分子决定因素在很大程度上仍然未知。在味觉受体细胞内发现的三类谷氨酸受体与响应氨基酸和核糖核苷酸的细胞信号传导相关：（i）TAS 1 R，（ii）代谢型-GluR，和（iii）离子型-NMDA受体。然而，它们各自在人类鲜味味觉感知中的作用尚不清楚。这项工作的长期目标是阐明人类对“鲜味”的感觉的遗传和分子机制。拟议项目的目标是澄清这三类受体的作用，以确定其他基因可能参与人类鲜味味觉感知，并在功能上测试与鲜味表型相关的变异受体。本提案的具体目标是： I.识别与鲜味盲症相关的变异基因和/或全基因组位点。二.表征与谷氨酸受体SNP相关的任何鲜味感知表型。三.在表达测定中定义变体谷氨酸受体刺激反应功能。 该提案将通过识别与人类蛋白质/氨基酸味道（鲜味）相关的基因来促进人类健康，随后将指导蛋白质营养不良人群的营养干预。味觉与营养有着重要的联系，因为我们接受或拒绝食物的决定最终取决于我们对食物味道的评估。因此，失去味觉的人，如放射治疗患者，在营养上受到影响。通常，发展中国家的儿童更喜欢高糖的食物，而不是其他类型的食物。在发展中国家，每两名儿童死亡中就有一名与饮食中蛋白质过少有关。由于蛋白质营养不良的儿童更喜欢在实验环境中添加游离氨基酸的食物，因此更好地了解氨基酸的味道机制可以指导设计更有食欲的食物，从而有助于减轻他们的营养不良。尽管它在饮食选择中的重要性，但人类的鲜味仍然是五种味觉品质中了解最少的一种，其遗传和分子决定因素在很大程度上仍然未知。我们将通过联合收割机结合人类感知、遗传学和分子受体功能的跨学科研究来表征候选鲜味受体和其他遗传位点的基因如何影响人类氨基酸味觉的感知属性。

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.