Human Umami Taste: Genetics of Psychophysical Traits

描述(由申请人提供)：氨基酸(特别是谷氨酸)的鲜味和甜度是两种令人胃口大开的味道，对我们健康地吸引蛋白质和碳水化合物(能量)大量营养素至关重要。胃口蛋白质口味系统可能面临的进化压力是我们的营养需求：获得膳食蛋白质来源对于生存至关重要，而夸希奥克(膳食蛋白质缺乏症)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很重要，但人类鲜味仍然是五种口味中最鲜为人知的一种，其遗传和分子决定因素在很大程度上仍不清楚。在味觉感受器细胞中发现了三类谷氨酸受体，它们与细胞对氨基酸和核苷酸的信号反应有关：(I)TAS1Rs，(Ii)代谢性GluRs和(Iii)离子性NMDA受体。然而，它们在人类鲜味知觉中各自的作用尚不清楚。这项拟议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。该项目的目标是阐明这三类受体的作用，识别可能与人类鲜味感知有关的其他基因，并从功能上测试与鲜味表型相关的不同受体。这项建议的具体目标是： 识别与尺侧失明相关的变异基因和/或全基因组基因座。鉴定与谷氨酸受体SNPs相关的任何手指知觉表型。在表达分析中定义不同的谷氨酸受体刺激反应功能。 这项建议将通过确定与人类蛋白质/氨基酸味道(Umami)相关的基因来促进人类健康，这将随后指导对蛋白质营养不良者的营养干预。味道与营养密切相关，因为我们对食物口味的评价最终决定了我们对食物的接受或拒绝。因此，失去味觉的人，如放射治疗患者，会受到营养方面的影响。通常，发展中国家的儿童更喜欢含糖量高的食物，而不是其他食物类型。在发展中国家，每两个儿童死亡中就有一个与饮食中蛋白质含量过低有关。由于蛋白质营养不良的儿童在实验环境中更喜欢添加了游离氨基酸的食物，因此对氨基酸味觉机制的更好理解可以指导设计出更有食欲的食物，从而帮助缓解他们的营养不良。尽管它在饮食选择中很重要，但人类鲜味仍然是五种口味中最鲜为人知的一种，其遗传和分子决定因素在很大程度上仍不清楚。我们将通过结合人类感知、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口味的感知属性。

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.