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增甜劑與甜味蛋白及其味覺受器

Sweeteners, sweet proteins and their taste receptor

摘要


甜味是人和其他生物體最喜愛的感覺之一。它在生活和營養狀況中扮演關鍵的角色。但追求甜味之餘往往會造成熱量過度的攝取,為了避免肥胖,許多低卡路里的增甜劑在過去不斷的被發展出來。自然和合成的增甜劑具有非常不同的化學架構,從糖到胺基酸,胜肽,蛋白質和其他化合物例如糖精。企求理性的設計高效之合成甜味劑,必需理解化學結構和甜味之間的關係。幾種模型被發展來解釋許多增甜劑的甜味測試之結果,包括甜度的增效作用。這些模型被使用來推斷增甜劑和受器之間的功能。但是這些模型都無法有效的說明為何甜味蛋白能夠擁有甜味。甜味產生的生物反應機制仍然是未知的。尤其是於味蕾上,被受器蛋白所協調接待的化學過程。直到最近,T_1R 受器,一個具專一味覺的C 型G 蛋白偶合的受器,才被提報出來,能協調哺乳動物之甜的味覺。T_1R_2 和T_1R_3 亞單位所形成的甜味受器,能辨認出完全不同的自然和合成的增甜劑。甜味化合物當與他們的受器可逆結合時,則會起動了甜味的訊號傳遞。人之T_1R_2 和T_1R_3 亞單位的結合產生了四個能與低分子量增甜劑結合的位置。甜味蛋白不容易接近這些結合位置,但是甜味蛋白能不進入深藏的孔穴而在其他位置與甜味受器相結合。這些論據顯示T_1R_3 和T_1R_2 扮演著不同的角色,以及甜味受器上存在著許多受質的結合位置。

並列摘要


Sweetness has been one of the most enjoyed tastes among humans and other species. It plays an important role in people’s life and nutritious effect. While indulging in sweetness, overeating on sugar can cause excessive calories intakes. To avoid obesity, a lot of low-calorie sweeteners have been developed. The chemical structures of natural sweeteners and synthetic ones are very different, ranging from sugars to amino acids, peptides, proteins and other compounds such as saccharin. To rationally design the novel synthetic sweeteners, it is necessary to understand the relationship between chemical structure and the elicitation of a sweet taste. Several models were developed to demonstrate the sweetening effect of sweeteners, including sweetness synergy. These models were used to infer the interaction between sweeteners and the receptors. Nevertheless, these models are unable to effectively explain the sweetening effect of the sweet taste protein. Their biological mechanism underlying the generation of sweet taste is still unclear. This is especially true on the chemoreception process mediated by receptor proteins on the taste buds. Until recently, the T_1R receptors, a family of taste-specific class C G protein coupled receptors, have been proposed to mediate mammals’ sweet tastes. The sweet taste receptors, formed by the T_1R_2 and T_1R_3 subunits, can recognize natural and synthetic sweeteners. The reversible binding of the sweet compounds to their receptors triggers the signal of the sweet taste. The combinations of the human T_1R_2 and T_1R_3 subunits yield four ligand binding sites for low-molecular-weight sweeteners. These sites are not easily accessible to sweet proteins, but sweet proteins can bind to a secondary site without entering those deep pinholes. These rationales indicate that the T_1R_3 and T_1R_2 play different roles, and there are many ligand binding sites on the sweet taste receptor.

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