“厚味”γ-谷氨酰-缬氨酸增味作用差异性机制

γ-谷氨酰-缬氨酸（γ-Glu-Val）具有多变的呈味特性,在水溶液中呈现涩味,可以增强基本味觉物质的味感强度,赋予奶酪、鸡汤、酱油等食物厚味味感。目前对于γ-Glu-Val呈味特性的机理研究甚少,尤其是鲜见它对于味觉增强效果的差异性机制的研究。本实验利用感官实验和分子模拟对γ-Glu-Val增味作用的差异性机制进行研究。感官实验结果显示,γ-Glu-Val对于基本味感（鲜味、甜味、咸味和酸味）均有一定的提升作用,而对于鲜味的提升效果最为明显。分子模拟实验的结果表明,γ-Glu-Val对基本味感受体（T1R1、T1R2和T1R3）均有一定的亲和力,其中对于鲜味受体T1R1的亲和力最强、结合自由能最高,与此相反,γ-Glu-Val对甜味受体T1R2的亲和力最弱、结合自由能最低,暗示其增鲜作用强于增甜作用。分子动力学结果显示,在味精存在的前提下,γ-Glu-Val可通过氢键和疏水键与鲜味受体T1R1上的氨基酸残基（Phe-274、Ser-275、Ser-300、Trp-303、Ala-147、Ala-170）相互作用,激活鲜味受体,以实现其增鲜作用。本实验解析了γ-Glu-Val增味作用差异性分子机制,为进一步验证其呈味机理提供理论支撑;同时为小分子物质的增味作用研究提供了思路。     

味觉感知的人体肠-脑轴信号传导机制研究进展

味觉是人类感知生物摄取能的重要环节,胃肠道亦存在味觉感知现象。本文从胃肠道味觉受体、胃肠道味觉感知通路及肠-脑轴味觉信号传导机制等方面进行了分析,胃肠道中味觉感知表明胃肠道中存在味觉受体第一家族亚型（taste receptor type 1 member,T1R）1、T1R2、T1R3、味觉受体第二家族亚型（taste receptors type 2,T2Rs）等味觉受体,且肠道味觉物质刺激肠内分泌细胞分泌胆囊收缩素（cholecystokinin,CCK）、肽YY（peptide YY,PYY）等脑肠肽激素,与味觉信号在神经元的传递有关;肠道中鲜味物质谷氨酸钠显著激活大脑缰核、杏仁核和下丘脑亚核的神经网络,表明肠-脑轴味觉感知是基于胃肠道受体及脑肠肽、神经元和大脑中枢神经系统之间的共同调控,从而提出肠-脑轴味觉信号传导机制假说,认为甜味受体T1R2/T1R3和鲜味受体T1R1/T1R3具有相似的信号传导通路,味觉物质作用于肠道后,与肠道中相应的味觉受体结合,激活磷脂酶-β2（phospholipase C-β2,PLC-β2）,释放Ca2＋,引起肠道内环境的变化,刺激肠内分泌细胞分泌PYY、CCK等激素,被肠神经元突触特异性识别,将味觉信号传导至大脑神经中枢;而谷氨酸代谢型受体4（metabotropic glutamate receptor 4,mGluR4）和苦味受体T2Rs信号传导通路则是通过激活磷酸二酯酶（phosphodiesterase,PDE）,使细胞质内3’,5’-环腺苷酸（3’,5’-cyclic adenylic acid,cAMP）浓度降低,从而解除环核苷酸（cyclic nucleotide,cNMP）的抑制作用,从而释放Ca2＋。基于肠-脑轴味觉偏好,为味觉发生改变的患者开发治疗新药物、寻找新的药物靶点提供了新的方向。对肠-脑轴味觉信号传导机制的研究将为胃肠道生理的神经控制提供分子框架、精准控制人体对味觉营养物质的生理反应,并对味觉物质在肠-脑轴中的摄入、代谢、调节等及开发新的味觉感知途径提供新的理论依据。     

A review of the associations between single nucleotide polymorphisms in taste receptors,eating behaviors,and health

Food preferences and dietary habits are heavily influenced by taste perception. There is growing interest in characterizing taste preferences based on genetic variation. Genetic differences in the ability to perceive key tastes may impact eating behavior and nutritional intake. Therefore, increased understanding of taste biology and genetics may lead to new personalized strategies, which may prevent or influence the trajectory of chronic disease risk. Recent advances show that single nucleotide polymorphisms (SNPs) in the CD36 fat taste receptor are linked to differences in fat perception, fat preference, and chronic-disease biomarkers. Genetic variation in the sweet taste receptor T1R2 has been shown to alter sweet taste preferences, eating behaviors, and risk of dental caries. Polymorphisms in the bitter taste receptor T2R38 have been shown to influence taste for brassica vegetables. Individuals that intensely taste the bitterness of brassica vegetables (“supertasters”) may avoid vegetable consumption and compensate by increasing their consumption of sweet and fatty foods, which may increase risk for chronic disease. Emerging evidence also suggests that the role of genetics in taste perception may be more impactful in children due to the lack of cultural influence compared to adults. This review examines the current knowledge of SNPs in taste receptors associated with fat, sweet, bitter, umami, and salt taste modalities and their contributions to food preferences, and chronic disease. Overall, these SNPs demonstrate the potential to influence food preferences and consequently health.     

Sweeteners

Abstract

Sweetness is always associated with emotive value judgments of what are thought to be liking, appreciation, attention, and reward. It has been shown that the ability to experience the sensation of sweetness is an inborn quality. Of the four basic taste sensations that can be experienced by man in chemoreception, sweetness has been studied the most exhaustively as to chemical structure‐taste relationships. Thus, in the last few decades a very large number of structurally unrelated compounds have been synthesized and evaluated for sweetness. This review summarizes the history of the discovery of sweeteners, the various receptor theories developed in the course of time, the transduction of taste, the neurophysiological mechanisms involved in sweet taste perception, the various sweet taste receptor sites, and the structure‐activity relations (SAR) explored so far. The authors subsequently discuss in detail the following classes of sweeteners: carbohydrates, nitro‐anilines, benzamides, amino acids, dipeptides, dihydrochalcones, flavonoids, isocoumarins, sulfamates, oximes, saccharins, acesulfames, urea derivatives, sesquiterpenes, diterpenes, triterpenes, and some sweet substances isolated from plants. On the basis of the present knowledge it can be concluded that there is more than one type of sweet taste receptor. It is expected that the rapid progress in molecular biology and X‐ray crystallography and the use of molecular modeling based on computer graphics will afford a deeper insight into the sweet taste perception mechanism in the near future.     

Interactions between umami and other flavor characteristics

Our understanding of the taste transduction mechanisms of umami substances is still in its infancy. However, evidence is now emerging that suggests that umami taste is perceived according to a receptor-mediated mechanism similar to those for sweet and bitter tastes. The synergistic interactions between glutamate and nucleotides appear to arise from an allosteric effect of nucleotides on a glutamate receptor. In some foods, umami substances appear to enhance the perceived sweetness or saltiness, or other flavor characteristics such as thickness and complexity, which may contribute to the ability of umami substances to improve overall palatability in certain foods.     

味觉受体研究热点分析

味觉是重要的感知反应，基本的味觉包括甜、酸、苦、咸、鲜5 种。味觉受体是用于感知各种味觉的蛋白质。本文对味觉受体热点关键词、来源、研究手段、受体类型、研究人员等进行分析概述，为开展味觉受体相关研究提供参考。通过文献分析发现，苦味、甜味、酸味、鲜味、大鼠、人类、小鼠、细胞、表达、蛋白质、诱导、基因、信号、神经元和分子等是味觉受体研究的热点关键词，Proceedings of the National Academy of Sciences、Journal of Neuroscience、American Journal of Physiology-Regulatory, Integrative and Comparative Physiology和Journal of Comparative Neurology是味觉受体研究领域的重点期刊。鼠类味觉受体是大多数实验的研究对象，然而鼠类和人类的味觉受体之间仍然存在较大差异，为更准确地探索人类味觉受体，还需对人类本身的味觉受体进行深入的研究。目前对味觉受体的研究已经进入结构生物学和神经生物学水平，主要采用分子生物学实验和计算机模拟技术等手段对受体结构进行探索。研究人员已经解析了青鳉鱼T1R2/T1R3配体识别结构域、斑马鱼Otop1和鸡Otop3的结构以及各味觉受体的信号传导通路，但大多数受体的精确结构还未解析出，也难以区分不同特点的味觉神经刺激。采用蛋白质表达纯化、蛋白质结构解析和信号传导等技术获得G蛋白偶联受体（G protein coupled receptors，GPCRs）的单晶体并解析晶体结构以及阐明各受体间的相互作用机理是目前重点的研究方向。美国目前在味觉受体研究领域处于领先地位，Ryba N. J. P.、Hoon M. A.和Chandrashekar J.等科学家目前引领了该领域的研究方向。本文明确了味觉受体领域发展现状，预测了味觉受体领域发展趋势，可为科研人员提供研究方向和思路。     

Sweet taste receptor expression in ruminant intestine and its activation by artificial sweeteners to regulate glucose absorption

Absorption of glucose from the lumen of the intestine into enterocytes is accomplished by sodium-glucose co-transporter 1 (SGLT1). In the majority of mammalian species, expression (this includes activity) of SGLT1 is upregulated in response to increased dietary monosaccharides. This regulatory pathway is initiated by sensing of luminal sugar by the gut-expressed sweet taste receptor. The objectives of our studies were to determine (1) if the ruminant intestine expresses the sweet taste receptor, which consists of two subunits [taste 1 receptor 2 (T1R2) and 3 (T1R3)], and other key signaling molecules required for SGLT1 upregulation in nonruminant intestines, and (2) whether T1R2-T1R3 sensing of artificial sweeteners induces release of glucagon-like peptide-2 (GLP-2) and enhances SGLT1 expression. We found that the small intestine of sheep and cattle express T1R2, T1R3, G-protein gustducin, and GLP-2 in enteroendocrine L-cells. Maintaining 110-d-old ruminating calves for 60 d on a diet containing a starter concentrate and the artificial sweetener Sucram (consisting of saccharin and neohesperidin dihydrochalcone; Pancosma SA, Geneva, Switzerland) enhances (1) Na⁺-dependent d-glucose uptake by over 3-fold, (2) villus height and crypt depth by 1.4- and 1.2-fold, and (3) maltase- and alkaline phosphatase-specific activity by 1.5-fold compared to calves maintained on the same diet without Sucram. No statistically significant differences were observed for rates of intestinal glucose uptake, villus height, crypt depth, or enzyme activities between 50-d-old milk-fed calves and calves maintained on the same diet containing Sucram. When adult cows were kept on a diet containing 80:20 ryegrass hay-to-concentrate supplemented with Sucram, more than a 7-fold increase in SGLT1 protein abundance was noted. Collectively, the data indicate that inclusion of this artificial sweetener enhances SGLT1 expression and mucosal growth in ruminant animals. Exposure of ruminant sheep intestinal segments to saccharin or neohesperidin dihydrochalcone evokes secretion of GLP-2, the gut hormone known to enhance intestinal glucose absorption and mucosal growth. Artificial sweeteners, such as Sucram, at small concentrations are potent activators of T1R2-T1R3 (600-fold > glucose). This, combined with oral bioavailability of T1R2-T1R3 and the understanding that artificial sweetener-induced receptor activation evokes GLP-2 release (thus leading to increased SGLT1 expression and mucosal growth), make this receptor a suitable target for dietary manipulation.     

Variation in human sweet taste receptor may result in different levels of sweet intensity variability between sweet stimuli

Understanding the physiological activation and genetic variation of the sweet taste receptor (T1R) can improve formula optimisation for products intended for a population of genetically diverse people. Computer modelling and cell culture techniques have thoroughly described the structure and binding sites of the T1R. The structure contains two subunits (T1R2 and T1R3) with multiple domains where sweet molecules can interact. The interaction takes place between individual molecules and amino acid residues of the T1R. The residues with which individual molecules interact differ between sweeteners. Person‐to‐person differences in the residue sequence of the T1R can arise from variation in the genes that encode the T1R, potentially effecting the function of the receptor. As a result of the specificity of the binding interactions, a specific genetic variation may affect sensitivity to some sweeteners, while sensitivity to other sweeteners remains normal. Therefore, it can be hypothesised that the level of person‐to‐person sweetness sensitivity variation may differ for each sweetener depending on the binding site of the molecule and site of T1R variation. The T1R structure, binding sites and genetic variation will be reviewed, as well as potential parameters to predict the degree of sensitivity variation and formulation strategies to minimise the effects of sensitivity variation.     

Cover Caption

April Online Cover : Taste transduction pathways for sweet, umami, and bitter taste (inspired by Luddi et al., 2019); the umami taste receptor; and anatomy of the human tongue (OpenStax Anatomy & Physiology, 2016), from “Molecular insights into human taste perception and umami tastants: A review” by Johan Diepeveen, Tanja C.W. Moerdijk-Poortvliet, Feike R. van der Leij. p. 1449–1465.     

The black agonist-receptor model of high potency sweeteners, and its implication to sweetness taste and sweetener design

The dose responses of the most commonly used high potency sweeteners (HPSs) have been measured by a more precise sensory procedure. The data were analyzed by Black's pharmacological model that takes into account not only agonist binding affinity but transduction efficiency as well. HPSs are clearly segregated into 2 groups depending on whether they bind to T1R2 or T1R3 of the receptor heterodimer. Surprisingly, the more potent sweeteners have lower transduction efficiencies. The implications of these on consumer product development and HPS design are discussed.     

A review of sweet taste potentiation brought about by divalent oxygen and sulfur incorporation.

The plethora of high-potency sweetener research has allowed the construction of important structure-taste relationships. In light of new structure-taste relationships, it is instructive to review sweet taste potentiation brought about by divalent oxygen and sulfur incorporation. The taste of sulfur-containing organic compounds was reviewed in Japanese by Yasuo Ariyoshi in 1977. Several new representative examples of sweet taste potentiation and taste dichotomy (sweet and bitter) found within similar classes of oxygen- and sulfur-containing organic compound: amides, dipeptides, ureas, sulfamates, sulfonamides, oximes, sugars, dihydroisocoumarins, and others are reviewed. Special attention is given to the thioethers and thioureas in sulfamates, dipeptides, aryl ureas, and hybrid dipeptide ureas. The most notable contributions have arisen from the work of Nofre and Tinti at Université Claude Bernard in Lyons, France. A common trend emerges with certain sweeteners when a carbon atom is strategically replaced by sulfur or oxygen atoms. The net result is an increase in the sweetness two- to tenfold. With saccharins, the usual bitter, metallic taste is removed. Sweet taste receptor models that have been published are mainly based on the original Shallenberger and Acree model of the glucophores AH-B with contributions from Kier (AH-B-X). AH is a proton donor group, B is a proton acceptor group, and X is some hydrophobic group. All of the models have overlooked the contributions of divalent sulfur (often in place of oxygen) in bringing about sweetness potentiation. There is no precedence for localizing the energy-minimized structures of sulfur-containing sweeteners in a binding mode that includes sulfur. These sulfur potentiation loci are analyzed and illustrated in a computer-generated sweetener model to show the specific region in which sulfur is being "recognized" as a potentiating feature.     

Taste transduction: Linkage between molecular mechanisms and psychophysics

Taste transduction is initiated when taste stimuli interact with receptor sites on the exposed apical microvilli of receptor cells. The interaction leads to an increase in intracellular Ca⁺⁺ and transmitter release from the taste cell. Recent studies have revealed that taste cells utilize a diversity of mechanisms for transduction. Ionic taste stimuli, such as salts and acids, interact directly with apically located ion channels to depolarize taste cells. In contrast, amino acids, sweeteners and most bitter tasting stimuli bind to specific membrane receptors that are usually coupled to G proteins and second messenger systems. This review summarizes recent progress in understanding the initial events in taste transduction. Commonalities of molecular mechanisms for different taste stimuli may help explain psychophysical interactions of taste stimuli.     

甜味分子的多点结合甜味理论

关于甜味分子生甜机理 ,存在 3种理论解释 ,分别为AH/B理论、AH/B/X理论和多点结合理论。实践证明 ,这 3种理论都能合理解释各类甜味物质的生甜机理。其中多点结合甜味理论认为 ,人体受体蛋白包含 8个基本的甜味识别部位 ,分别为B、AH、XH、G1、G2、G3、G4和D ,它们与甜味分子相应的结合部位发生相互作用 ,受体蛋白由紧密的收缩构象改变为开放的展开构象 ,从而产生甜味刺激传导 ,甜味产生后 ,由于识别部位的极性或离子基团之间的静电作用力 ,将驱散甜味分子 ,使受体蛋白恢复原来的收缩构象。根据这一理论 ,可以合理构造各种糖分子及其衍生物的多点结合模型。蔗糖是B1、B2、AH1、AH2、XH1、XH2、G1、E1、G2、E2、G3、E3、G4、E4型甜味剂 ,D 葡萄糖是B1、B2、AH1、AH2、XH1、XH2型甜味剂 ,D 果糖是E1、E2、E3、E4型甜味剂。     

The chemistry and physiology of sour taste--a review

ABSTRACT:  Sour taste is the key element in the flavor profile of food acidulants. Understanding the chemistry and physiology of sour taste is critical for efficient control of flavor in the formulation of acid and acidified foods. After a brief introduction to the main applications of food acidulants, several chemical parameters associated with sour taste are discussed. Special emphasis is given to hydrogen ions, protonated (undissociated) acid species, titratable acidity, anions, molar concentration, and physical and chemical properties of organic acids. This article also presents an overview of the physiology of sour taste and proposed theories for the transduction mechanisms for sour taste. The physiology of sour taste perception remains controversial and significant diversity exists among species with regard to cellular schemes used for detection of stimuli. The variety of mechanisms proposed, even within individual species, highlights the complexity of elucidating sour taste transduction. However, recent evidence suggests that at least one specific sour taste receptor protein has been identified.     

Effects of proteolysis on the sensory properties of the sweet protein,thaumatin

We have examined the effects of different proteases on the sensory properties of the sweet protein, thaumatin. Trypsin and thermolysin, proteases with quite different primary specificities, have little effect upon the sweetness of ihaumatin, although in each instance the protein has been extensively cleaved. The retention of the sweet taste is probably due to the disulphide bridge cross-linking which serves to maintain the overall structure of the molecule even when it has incurred proteolytic cleavages. By contrast, subtilisin and chymotrypsin effect greater digestion, to the extent that the protein is reduced to small peptides even when the disulphide bridges are intact. Under these circumstances the sweet taste is lost. The sensory properties of thaumatin depend upon the maintenance of a part of the polypeptide chain in a particular conformation.     

On the Effect of Tastant Excluded Fillers on Sweetness and Saltiness of a Model Food

ABSTRACT: In this study, the effect on taste due to the addition of air bubbles to a water-based gel was investigated. The gel phase contained either sucrose to give a sweet taste or sodium chloride to give a salty taste. For the sweet gels, taste intensities were evaluated for samples with different volume fractions of the air bubbles (up to 40%, v/v) and different concentrations of the sucrose. For the salty gels, samples were evaluated at 40% volume fraction of air bubbles. It was found that a reduction of the sodium chloride or sucrose by the same weight percentage as the volume fraction of the air bubbles in the samples gave equal taste perception as the nontastant-reduced samples. Moreover, saltiness and sweetness perception were clearly enhanced at 40% volume fractions of air bubbles if the sodium chloride or sucrose was not reduced. Thus, the overall tastes of the samples appeared to depend mainly on the concentration levels of the salt or the sucrose in the aqueous phase irrespective of the volume fraction of the air bubbles. However, the air bubbles were found to change the texture and appearance of the samples. It has been demonstrated that the inclusion of air bubbles offers scope for the reduction of sodium chloride or sucrose in food products.     

Correlation between in vitro binding activity of sweeteners to cloned human sweet taste receptor and sensory evaluation

Food Science and Biotechnology - The human sweet taste receptor is a TAS1R2/TAS1R3 heterodimer. To investigate the correlation between the in vitro affinity of sweeteners with stably expressed...     

Species differences toward sweeteners

The understanding of the sense of taste in mammals has over the last few decades slowly changed from the misconception that all mammals are equal with regard to taste to a realization that there are profound differences between species. These differences probably pertain to all basic tastes, but have been especially documented with regard to the sweet taste. This study addresses two issues: the difference in taste fiber specificity between mammals and the related issue of species differences in ability to taste sweeteners. These issues are illustrated by single taste fiber recordings from hamster, pig, rhesus monkey and chimpanzee. The hamster, a rodent, is used as an animal model in taste research because of its especially well developed sweet taste sensitivity, but this study shows that many sweeteners do not taste sweet to the hamster. The same is true for the pig, an ungulate, and from this point of view quite unrelated to the human, but with similar internal anatomy, food preferences and diets, and therefore extensively used as an animal model. Even the rhesus monkey, an old world primate belonging to the same superfamily as human, Catarrhina, shows some differences in its sweet tasting ability and taste fibers specificity although much less so than the previously mentioned species. The only species in which studies of its sense of taste have not yet revealed any differences from the human sense of taste, is the chimpanzee, which by most accounts is our closest relative.     

Effect of ideal–relative sweetness on yogurt consumption

The objectives of this study were to determine how hedonically different sweetness levels in yogurt, determined by the ideal–relative rating method, affected taste test liking ratings and consumption in a naturalistic setting. Nineteen subjects attended a preliminary session, a taste test and three lunch tests. During the taste test, they rated yogurt with three levels of sweetness (high, optimum, and low) for six attributes. During each lunch test, they were offered a tray of nine food items, including yogurt at one of the three sweetness levels. Subjects liked the optimally sweet yogurt best in the taste test and consumed the most of it at lunch. Taste test liking ratings did not predict the amount of yogurt consumed during lunch. The lower-than-optimum sweetness level was more detrimental to taste test ratings than was the oversweetened yogurt whereas the higher-than-optimum sweetness level was more detrimental to consumption during lunch than was the undersweetened yogurt.