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Modulation of Sweet Taste by Umami Compounds via Sweet Taste Receptor Subunit hT1R2

机译:鲜味化合物通过甜味受体亚基hT1R2对甜味的调节

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摘要

Although the five basic taste qualities—sweet, sour, bitter, salty and umami—can be recognized by the respective gustatory system, interactions between these taste qualities are often experienced when food is consumed. Specifically, the umami taste has been investigated in terms of whether it enhances or reduces the other taste modalities. These studies, however, are based on individual perception and not on a molecular level. In this study we investigated umami-sweet taste interactions using umami compounds including monosodium glutamate (MSG), 5’-mononucleotides and glutamyl-dipeptides, glutamate-glutamate (Glu-Glu) and glutamate-aspartic acid (Glu-Asp), in human sweet taste receptor hT1R2/hT1R3-expressing cells. The sensitivity of sucrose to hT1R2/hT1R3 was significantly attenuated by MSG and umami active peptides but not by umami active nucleotides. Inhibition of sweet receptor activation by MSG and glutamyl peptides is obvious when sweet receptors are activated by sweeteners that target the extracellular domain (ECD) of T1R2, such as sucrose and acesulfame K, but not by cyclamate, which interact with the T1R3 transmembrane domain (TMD). Application of umami compounds with lactisole, inhibitory drugs that target T1R3, exerted a more severe inhibitory effect. The inhibition was also observed with F778A sweet receptor mutant, which have the defect in function of T1R3 TMD. These results suggest that umami peptides affect sweet taste receptors and this interaction prevents sweet receptor agonists from binding to the T1R2 ECD in an allosteric manner, not to the T1R3. This is the first report to define the interaction between umami and sweet taste receptors.
机译:尽管可以通过各自的味觉系统识别五种基本口味品质(甜,酸,苦,咸和鲜味),但是在食用食物时通常会经历这些口味品质之间的相互作用。具体而言,已经研究了鲜味是否增强或降低了其他味觉形式。但是,这些研究是基于个人的认知而不是分子水平的。在这项研究中,我们在人中使用包括味精(MSG),5'-单核苷酸和谷氨酰二肽,谷氨酸-谷氨酸(Glu-Glu)和谷氨酸-天冬氨酸(Glu-Asp)在内的鲜味化合物,研究了鲜味与甜味的相互作用。甜味受体hT1R2 / hT1R3表达细胞。蔗糖对hT1R2 / hT1R3的敏感性被MSG和鲜味活性肽显着减弱,而鲜味活性核苷酸则没有。当甜味受体被靶向T1R2的细胞外结构域(ECD)的甜味剂(例如蔗糖和乙酰磺胺酸钾而不是甜蜜素)激活时,甜味受体被味精和谷氨酰胺肽抑制的作用很明显,甜味剂与T1R3跨膜结构域相互作用( TMD)。将鲜味化合物与乳糖吡唑(靶向T1R3的抑制药物)一起使用时,会产生更严重的抑制作用。还观察到F778A甜受体突变体的抑制作用,该突变体在T1R3 TMD功能上有缺陷。这些结果表明鲜味肽影响甜味受体,并且这种相互作用阻止甜味受体激动剂以变构方式而不是T1R3与T1R2 ECD结合。这是第一个定义鲜味和甜味受体之间相互作用的报告。

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