臺灣博碩士論文加值系統

眾所周知茶的酚類化合物是具有保健作用，且同時可引起類似鮮味的複雜味覺。相較原型鮮味化合物，味精(monosodium glutamate, MSG)，誘發中國餐館綜合症，而這些茶酚類物質，可以作為味精的健康替代品。根據上述考量，我們採用分子對接模擬(molecular docking simulation)尋找在茶飲品中可能的具有鮮味的酚類物質。為研究方便起見，鮮味受體如T1R1，利用同源建模(homology modeling)方法建構。對接結果顯示，確實有些茶酚類化合物可以作為鮮味配體而且某些酚類化合物可做為增強劑來協同增強鮮味。這些具鮮味的茶酚類化合物可以引發鮮味感覺的分子機制與味精和其增強劑是相同。然而任何主要茶葉的酚類化合物，如EGCG，並不能引起相同的鮮味感覺。無論誘導健身，鮮味的茶酚類化合物和受體分子之間的細部的相互作用與誘導附合(induced fitness)昰與原型的鮮味的化合物和受體間的作用有明顯差異。由此可見，茶酚類化合物可作為食品調味劑和同時亦可作為抗氧化劑。

The phenolic compounds of tea are known to responsible to both the healthy effects and complex umami-like taste sensation. Compared to the prototypical umami compound, monosodium glutamate (MSG), with notorious Chinese Restaurant Syndrome, these tea phenolics can act as a healthy substitute. With the above consideration, we performed a molecular docking simulation to search the possible umami phenolics in tea beverages. To facilitate the investigation, umami receptor, such as T1R1, was constructed through homology modeling. The docking results suggested that several tea phenolic compounds can act as umami ligands and some other phenolic compounds can synergistically augmented the umami taste as enhancers. These tea phenolic compounds can trigger the umami sensation through the same molecular mechanism by MSG and its enhancers. However the umami sensation can not be equivalently replaced with any of the major tea phenolic compounds, such as Epigallocatechin gallate (EGCG). Regardless the induced fitness, the detailed molecular interactions between the tea umami phenolic compounds and the receptor were drastically different from those of prototypical umami compounds and the receptor. It seems that the tea phenolic compounds may be developed as a food-flavoring agents and antioxidants at the same time.

Contents
謝誌 i
中文摘要 iii
Abstract iv
Chapter 1 1
Introduction 1
Chapter 2 5
MODEL AND METHODS 5
2.1 Homology modeling 5
2.1.1 Introduction of homology modeling 5
2.2 Computation method 7
2.2.1 Molecular modeling 7
2.2.2 Molecular docking procedure 15
Chapter 3 16
Results and Discussions 16
3.1 Molecular docking of L-glutamate and IMP 16
3.1.1 The orientation and interaction pattern of the ligand and enhancer inside the docking domain 17
3.1.2. Molecular docking with theogallin and gallic acid as enhancers 20
3.2 Molecular modeling of putative umami compounds in tea fusion 21
3.2.2 Key residues for umami receptor activity 26
3.2.3 Flexibility in Docking of ligand and enhancer pair to the umami receptor 30
3.3 Docking of catechins to the umami receptor 32
3.4 Docking of tea flavonol compounds to the umami receptor 35
Chapter 4 38
Conclusion 38
Reference 39

1.Chaudhari N, Landin AM, Roper SD: A novel metabotropic glutamate receptor functions as a taste receptor. Nature Neurosci 2000, 3:113-119
2.Nelson G, Chandrashekar J, Moon MA, Feng L, Zhao G, Ryba NJ, Zucker CS: An amino-acid taste receptor. Nature 2002, 416:199-202.
3.YamaguchiS., Ninomiya K. umami and food palatability J Nutr. 130, 9215-9265 2000
4.Raiten DJ, Talbot JM, Fisher KD (1995). "Executive Summary from the Report: Analysis of Adverse Reactions to Monosodium Glutamate (MSG)". Journal of Nutrition 125 (11): 2892S-2906S.
5.Geha, R., Beiser, A., Ren, C., Patterson, R., Greenberger, P., Grammer, L.C., Ditto, A.M., Harris, K.E., Shaughnessy, M.A., Yarnold, P., Corren, J., Saxon, A. Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebocontrolled study. The Journal of Nutrition, 130:1058S-1062S, 2000.
6.Chandrashekar J., Hoon MA, Ryba NJ, Zuker CS, the receptors and cells for mammalian taste Nature 444, 288-294 2006.
7.Zhang, F., Klebansky, B., Fine, R. M., Xu, H., Pronin, A., Liu, H., Tachdjian, C., & Li, X. (2008). Molecular mechanism for the umami taste synergism. Proceedings of the National Academy of Science of the United States of America, 105, 20930-200934.
8.Behrens M, Meyerhof W, Hellfritsch C, Hofmann T. Sweet and umami taste: natural products, their chemosensory targets, and beyond. Angew Chem Int Ed Engl. 2011 Mar 1;50(10):2220-42
9.Li X, Staszewski L, Xu H, Durick K, Zoller M & Adler E (2002) Human receptors for sweet and umami taste. Proc Natl Acad Sci U S A 99, 4692-4696.
10.Temussi PA (2009) Sweet, bitter and umami receptors: a complex relationship. Trends Biochem Sci 34, 296-302.
11.Zhang, F., Klebansky, B., Fine, R. M., Xu, H., Liu, H., Servant, G., Zoller, M., Tachdjian, C., & Li, X. (2010). Molecular mechanism of the sweet taste enhancers. Proceedings of the National Academy of Science of the United States of America, 107, 4752-4757.
12.N. Kunishima, Y. Shimada, Y. Tsuji, T. Sato, M. Yamamoto, T. Kumasaka, S. Nakanishi, H. Jingami, K. Morikawa, Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor, Nature 407 (2000) 971–977.
13.Tsuchiya D, Kunishima N, Kamiya N, Jingami H & Morikawa K (2002) Structural views of the ligand-binding cores of a metabotropic glutamate receptor complexed with an antagonist and both glutamate and Gd3+. Proc. Natl. Acad. Sci. USA 99, 2660-2665
14.T. Muto, D. Tsuchiya, K. Morikawa, H. Jingami, Structures of the extracellular regions of the group II/III metabotropic glutamate receptors, Proc. Natl. Acad. Sci. USA 104 (2007) 3759–3764
15.M. Noguchi, S. Arai, M. Yamashita, H. Kato, M. Fujimaki, J. Agric. Food Chem. 1975, 23, 49 – 53
16.K. Maehashi, M. Matsuzaki, Y. Yamamoto, S. Udeka, Biosci. Biotechnol. Biochem. 1999, 63, 555 – 559.
17.Haslam, E. (2003). Thoughts on thearubigins. Phytochemistry, 64, 61–73
18.Sakato, Y. Studies on the chemical constituents of tea. Part III. On a new amide theanine (in Japanese). Agric. Chem. Soc. Jpn. 1950, 23, 262-267
19.Kaneko, S.; Kumazawa, K.; Masuda, H.; Henze, A.; Hofmann, T. Molecular and Sensory Studies on the Umami Taste of Japanese Green Tea. J. Agric. Food Chem. 2006, 54, 2688–2694.
20.Horie, H.; Ujihara, T.; Kohata, K. Analysis of tasty nucleotides in green tea Infusions (in Japanese). Tea Res. J. 2002, 93, 55-61.
21.Lee, V. S. Y., Dou, J., Chen, R. J. Y., Lin, R. S., Lee,M. R., & Tzen, J. T. C. (2008).Massive accumulation of gallic acid and unique occurrence of myricetin, quercetin and kaempferol in preparing old oolong tea. Journal of Agricultural and Food Chemistry, 56, 7950–7956
22.Lee, R. J., Lee, V. S., Tzen, J. T. C., & Lee, M. R. (2010). Study of the release of gallic acid from (−)-epigallocatechin gallate in old oolong tea by mass spectrometry Rapid Communications in Mass Spectrometry, 24, 851–858
23.H. Van derWel, K. Loeve, Eur. J. Biochem. 1972, 31, 221– 225
24.Rice-Evans, C., Miller, N., & Paganga, G. (1997). Antioxidant properties of phenolic compounds. Trends in Plant Science, 2, 152–159
25.Aaby, K., Hvattum, E., & Skrede, G. (2004). Analysis of flavonoids and other phenolic compounds using high-performance liquid chromatography with coulometric array detection: Relationship to antioxidant activity. Journal of the Agricultural and Food Chemistry, 52, 4595–4603
26.Luo, Y., Cai, Q., Sun, M., & Corke, H. (2004). Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Science, 74, 2157–2184
27.Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M. CHARMM: A program for macromolecular energy minimization and dynamics calculations. J Comp Chem 1983; 4: 187-217