研究生: |
吳秀珠 |
---|---|
論文名稱: |
利用二維形體篩分/逆相層析法配合感應耦合電漿質譜法及電灑質譜法進行兔子血清及營養補充液中含銅、鋅、鎘、鈷等元素之生物分子的鑑定研究 Characterization of Cu, Zn, Cd, Co-containing Biomolecules in Rabbit Serum and Supplement by 2D SEC/RPLC Chromatographic Techniques coupled with ICP-MS and ESI-MS Detection |
指導教授: |
楊末雄博士
孫毓璋博士 |
口試委員: | |
學位類別: |
碩士 Master |
系所名稱: |
原子科學院 - 生醫工程與環境科學系 Department of Biomedical Engineering and Environmental Sciences |
論文出版年: | 2005 |
畢業學年度: | 93 |
語文別: | 中文 |
論文頁數: | 146 |
中文關鍵詞: | 金屬生物分子 、感應耦合電漿質譜法 、電灑質譜法 、二維液相層析法 、金屬硫蛋白 |
外文關鍵詞: | metal-binding biomolecule, ICP-MS, ESI-MS, 2D SEC/RPLC, MT |
相關次數: | 點閱:1 下載:0 |
分享至: |
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
由於含微量元素之生物分子在生物體內扮演著許多重要的生化功能,相關的研究工作近年來業已成為分析化學領域中的一個重要的研究主題。但由於生物體內含有微量元素的生物分子通常係以極低濃度存在,且生物樣品的基質十分複雜,致使在分析方法之發展上仍有諸多困難尚待克服。
本研究研究的目的旨在建立一套二維形體篩分/逆相層析技術,並配合感應耦合電漿質譜法及電灑質譜法,進行口服液樣品及血清樣品中含金屬分子(metal-binding biomolecule)之鑑定工作。在評估所欲建立之分析系統對含有特定微量元素之生物分子鑑定能力的過程中,有鑑於文獻中有關金屬硫蛋白分子的研究已相當透徹,因此於方法建立之初,本研究係選擇金屬硫蛋白(metallothionein, MT)來進行方法可行性的研究。在確立所欲建立分析方法的可行性之後,本研究亦嘗試利用所建立之分析程序,試圖探求其在鑑定兔子血清中含有Cu,Zn,Co等元素之生物分子時可能遭遇之困難及適用性。
根據目前所獲致之實驗結果可知,本研究所開發之2D-SEC/RPLC層析系統,已可順利地鑑定出口服液樣品及兔子血清樣品中的金屬硫蛋白分子及維生素B12分子。但受到RPLC-ESI-MS偵測的靈敏度及RPLC分離效果的限制,目前仍無法確定地鑑定出血清樣品中含銅及鋅的生物分子。為克服上述分析技術上的限制,未來應可藉由提高濃縮倍數,增進RPLC分離純化效果及改用更為靈敏以及具有更寬mass range的分子鑑定技術來達成鑑定生物體內金屬蛋白的目的。
1-1 D. M. Templeton, Fresenius J. Anal. Chem., 363, 505 (1999)
1-2 Rita Cornelis, “Analysis of Clinical and Laboratory Science”, 26, 3, 252 (1996)
1-3 W. Windisch, Anal. Bioanal. Chem., 372, 421 (2002)
1-4 G. Berthon, “Handbook of Metal-ligand Interactions in Biological Fluids”, Marcel Dekker Inc (1995)
1-5 R. Lobinski, J. Szpunar, Anal.. Chim. Acta., 400, 321 (1999)
1-6 A. Sanz-Medel, Spectrochimica. Acta. PartB, 53, 197 (1998)
1-7 R. Corniels, H. Crews, O. F. Donard, L. Ebdon, Ph. Quevauviller, Fresenius. J. Anal. Chem.,370:120 (2001)
1-8 A. N. Richarz, P. Bratter, Anal. Bioanal. Chem., 372, 412 (2002)
1-9 Anal. Chem., 72, 1, June 1, 412A (2000)
1-10 W. M. Becker, J. B. Reece, M. F. Poenie, The World of the Cell 3th, the Benjamin/Cummings Publishing Company (1996)
1-11 A. Makarov, J. Szpunar, J. Anal. At. Spectrom., 14, 1323 (1999)
1-12 R. Forrer, K. Gautschi, H. Lutz, Biological Trace Element Research, 80, 77 (2001)
1-13 B. A. Fowler, Environmental Healthy Perspectives, 100, 57 (1992)
1-14 J. Szpunar, Anal. Bioanal. Chem., 373, 404-411 (2002)
1-15 J. Szpunar, R. Lobinski, Pure Appl. Chem., 71, 5, 899-918 (1999)
1-16 環境生物無機化學, 淑馨出版社,彭安/王文華 (1993)
1-17 http://www.vghtpe.gov.tw/~biochem/SOP/Cu.htm
1-18 http://www.ht.org.tw/care/food/food4_6.htm
1-19 http://www.healthhouse.com.tw/info/minerals/zinc.htm
1-20 The USP GUIDE TO VITAMINS & MINERALS(by authority of U.S Pharmacopeia)
1-21 吃的學問--你吃下多少維生素?,黃伯超/廖偉宗,67-75
1-22 水溶性維生素的影響,長春月刊,鄭金寶著,62-67
1-23 醫藥日報,張意宜,民國85.7.16~7.20
1-24 營養學,東華出版社,黃蔭樨/李漢芳,民國78年
1-25 實用營養學,華杏出版社,趙玫珺/陳維昭,民國78年
1-26 國民營養指導手冊(二),行政院衛生署編
1-27 營養與健康,正中出版社,陳昌平
1-28 營養學,茂昌出版社,宋申審,民國80年
1-29 營養學精要(11版),黃柏超/游素玲著,民國79年
1-30 臨床藥局與維生素、營養補充劑(臨床藥局系列報導),李榮輝,民國82年
1-31 普通營養學(二版),匯華出版社,王果行/邱志威/張樂綺/盧義發/蔡敬民,民國82年
1-32 H. Haraguchi, J. Anal. At. Spectrom., 19, 1, 8 (2004)
1-33 H. Sakusai, H. Tanaka,“Bio-trace Elements”, Nankodo, Tokyo (1996)
1-34 H. Haraguchi, H. Matsura, Proceedings of International Symposium on Bio-trace Elements 2002, (BITRE 2002), eds. S. Enomoto, Y. Seko, The Institute of Physical and Chemical Research (RIKEN), Wako, 3-8 (2003)
1-35 M. P. Richards, J. H. Beattie, J. Cap. Electrophoresis 1, 196 (1994)
1-36 M. P. Richards, J. H. Beattie, J. Chromatogr., 648, 459 (1993)
1-37 G. Bordin, F. C. Raposo, A. R. Rodriguez, Can. J. Chem., 72, 1238 (1994)
1-38 R. Lobinski, H. Chassaigne, J. Szpunar, Talanta, 46, 271 (1998)
1-39 V. Virtanen, G. Bordin, A. R. Rodriguez, J. Chromatogr. A, 734, 391 (1996)
1-40 M. J. Stillman, Coord. Chem. Rev., 144, 461 (1995)
1-41 J. H. R. Kägi, in:K. T. Suzuki, N. Imura, M. Kimura (Eds.), Metallothionein III: Biological Roles and Medical Implications, Birkhauser, Boston, 29-55, 1993
1-42 A. H. Robbins, D. E. McRee, M. Williamson, S. A. Collett, N. H. Xuong, W. F. Furey, B. C. Wang, C. D. Stout, J. Mol. Biol., 221, 1269 (1991)
1-43 A. H. Robbins, C. D. Stout, in M. J. Stillman, C. F. Shaw III, K.T. Suzuki (eds.), Metallothioneins, VCH, New York, 3, 31-54 (1992)
1-44 W. Braun, M. Vasak, A. H. Robbins, C. D. Stout, G. Wagner, J. H. K. Kagi, K. Wuthrich, Proc. Natl. Acad. Sci. USA., 89, 10124 (1992)
1-45 S. Choudhuri, J. M. Jr. McKim, C. D. Klassen, Toxicol. Appl. Pharmacol. 166, 117 (1992)
1-46 M. Margoshes, B. L. Vallee, J. Am. Chem. Soc.,79, 4813 (1957)
1-47 http://www.vghtpe.gov.tw/~biochem/SOP/Cu.html
1-48 G. J. Opitech, J. W. Jorgenson, R. J. Anderegg, Anal. Chem., 69, 13, 2283-2291 (1997)
1-49 C. Kent, “Basic of Toxicology”, John Wiely & Sons, Inc (1998)
1-50 http://wantan.tacocity.com.tw/wantan/imfor/imfor13.htm
1-51 H. Haraguchi, Bull. Chem. Soc. Jpn., 72, 163-1186 (1999)
1-52 J. Szpunar, Analyst, 125, 963-988 (2000)
1-53 M. Montes-Bayon, K. DeNicola, J. A. Carso, J. Chromatogr. A, 1000, 457-476 (2003)
1-54 J. Szpunar, R. Lobinski, A. Prange, Appl. Spectrosc., 57, 102A-112A (2003)
1-55 H. Tao, Bunseki Kagaku, 46, 239-263 (1997)
1-56 J. Szpunar, S. McShsshy, K. Poles, V. Vacchina, S. Mounicou, I. Rodriguez, R. Lobinski, Spectrochim. Acta, 55, 779-793 (2000)
1-57 J. R. Ecinar, L. Querdane, W. Buchmann, J. Tortajade, R. Lobinski, J. Szpunar, Anal. Chem., 75, 3765-3774 (2003)
1-58 S. McShsshy, M. Marcinek, H. Chassaigne, J. Szpunar, Anal. Chim. Acta, 410, 71-84 (2000)\
1-59 K. Palec-Pawlak, D. Schaumloffel, J. Szpunar, A. Prange, R. Lobinski, J. Anal. At. Spectrom., 17, 880-886 (2002)
1-60 E. Rosenberg, J. Chromator. A, 1000, 841-889 (2003)
2-1 J. Porath, P. Flodin, Nature, 183,1657 (1959)
2-2 G. B. Irvine, Analytical Chemica Acta, 352,387 (1997)
2-3 Chi-san Wu, “Handbook of Size Exclusion Chromatography”, Marcel Dekker Inc, 2 (1995)
2-4 Uwe D. Neue, “HPLC Columns”, Wiley-Vch, 157 (1997)
2-5 K. E. Jarvis, A. L. Gray, R. S. Houk, “Handbook of Inductively coupled Plasma Mass Spectrometry”, 15,17 (1994)
2-6 Richard B. Cole, “Electrospray Ionization Mass Spectrometry”, John Wiley & Sons, Inc, (1997)
2-7 P. Kebarle, Journal of Mass Spectrometry, 35,804 (2000)
2-8 API service video traning procedures, Operator’s Manual, PE SCIEX, Inc
2-9 R. Martin Smith, Kenneth L. Busch, “Understanding Mass Spectrometry-A Basic Approach”, John Wiley & Sons, Inc, (1999)
2-10 李美貴,國立清華大學化學研究所博士班論文 (1995)
2-11 Feng, et. al. Anal. Chem., 64, 2090 (1992)
2-12 A. T. Ganguly, B. N. Preanlis, A. Tsarbopoulous, T. R. Covey, E. Huang, S. A. Fuhrman, J. Am. Chem. Soc., 114,6559 (1992)
2-13 S. Akashi, U. Niitsu, R. Yuji, H. Ide, K. Hirayama, Biomed. Environ. Mass spectrum., 22, 124 (1993)
2-14 B. Ganem, Y. T. Li, J. D. Henion, J. Am. Chem. Soc., 113, 6294 (1991)
2-15 Stevenson C. L., et. al. J. Am. Soc. Mass Spectrom., 4, 646 (1993)
2-16 T. Ohmi, J. B. Fenn, J. Am. Chem. Soc., 114, 3241, (1992)
2-17 G. J. Van Berkel, K.G. Asano, Anal. Chem., 66, 2096 (1994)
2-18 S. R. Wilson, Y. Wu, J. Am. Soc. Mass Spectrom., 4,596 (1993)
2-19 K. Hiraoka, I. Kudaka, S. Fujimaki, H. Shinohara, Rapid Commun. Mass Spectrom., 6, 254 (1992)
2-20 Katta, S. K. Chowdhury, B. T. Chiat, J. Am. Chem. Soc., 112, 5348 (1990)
2-21 P. Jayaweera, A. T. Blades, M. G. Ikonomou, P. Kebarle, J. Am. Chem. Soc., 112, 2452 (1990)
2-22 A. P. B. Bruins, J. Chromatogr., 554, 39 (1991)
2-23 D. C. Liebler, Introduction to Proteomics-Tools for the New Biology , Humana Press Inc., 55~76 (2002)
2-24 L. R. Snyder, J. J. Kirkland, “Introduction to modern liquid chromatography” (1979)
2-25 Training course, “Liquid Chromatography School”, Waters
2-26 B. A. Bidlingmeyer, J. Chromatographic Science., 18, 525 (1980)
2-27 張瑞玫,國立清華大學原子科學研究所碩士班論文 (2000)
2-28 詹富閔,國立清華大學原子科學研究所碩士班論文 (2002)
2-29 H. P. J. Bennett, J. Chromatogr.,226, 501 (1983)
2-30 K. Hunter, At. Spectrosc., 15, 17 (1994)
2-31 A . TOMLINSON, J.R. VANE, J.A. MITCHELL, I . APPLETON, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA , 91, 2046-2050 (1994)
4-1 詹富閔,國立清華大學原子科學研究所碩士班論文 (2002)
4-2 張瑞玫,國立清華大學原子科學研究所碩士班論文 (2000)
4-3 K. E. Jarvis, A. L. Gray, R. S. Houk, “Handbook of Inductively Coupled Plasma Spectrometry”, Blackie & Son Ltd. (1992)
4-4 A. Montaser,“Inductively Coupled Plasma Spectrometry”, Wiley-VCH Inc (1998)
4-5 B. Gercken. R. M. Barnes, Anal. Chem., 63, 283 (1991)
4-6 S. C. K. Shum, R. S. Houk, Anal. Chem., 65, 2972 (1993)
4-7 K. A. High, J. S. Bials, A. J. Methven, J. W. McLaren, Analyst, 120, 625 (1995)
4-8 K. A. High, B. A. Methven, J. W. McLaren, K. W. M. Siu, J. Wang, J. F. Klaverkamp, J. S. Bials, Fresenius J. Anal. Chem.,351, 393 (1995)
4-9 K. Takatera, T. Watanbe, Anal. Sci.,8,469 (1992)
4-10 J. Szpunar, H. Chasaigne, O. Donard, J. Battmer, R. Lobinski, In Applification of Inductively Coupled Plasma Spectrometry (G. Holland, ed.), RSC (1997)
4-11 K. T. Suzuki, S. Yoneda, M. Itoh, M. Ohmichi, J. Chromator. Biomed. Appl., 670, 63 (1995)
4-12 K. T. Suzuki, Tohokou J. Exp. Med., 178, 27 (1996)
4-13 K. T. Suzuki, M. Itoh, M. Ohmichi, Toxicology, 103, 157 (1995)
4-14 K. T. Suzuki, M. Itoh, M. Ohmichi, J. Chromator. Biomed. Appl., 666, 13 (1995)
4-15 J. Szunar, T. Pieper, A. Markarov, B. Keppler, R. Lobinski, Anal. Chem. Acta, 387, 135 (1999)
4-16 K. T. Suzuki, Analusis Magzine, 26, N 6 (1998)
4-17 環境生物無機化學, 淑馨出版社 (1992)
4-18 S. Choudhuri, J. M. Jr. McKim, C. D. Klassen, Toxicol. Appl. Pharmacol. 166, 117 (1992)
4-19 R. Lobinski, H. Chassaigne, J. Szpunar, Talanta, 46, 273 (1998)
4-20 B. Michalke, P. Schramel, J. Trace Elem. Electrolytes Health Dis., 4, 163 (1990)
4-21 K. Guenther, H. Waldner, Anal. Chem. Acta, 256, 165 (1992)
4-22 A. Mazzucotelli, A. Viarengo, L. Canesi, E. Ponzano, P. Rivaro, Analyst, 116, 605 (1991)
4-23 O. M. Steinebach, H. T. Wolterbeek, Chromatogr. Biomed. Appl., 130, 199 (1993)
4-24 M. Apostolova, P. R. Bontchev, C. Nachev, I. Sirakova, J. Chromatogr., B. Biomed. Appl., 131,191 (1993)
4-25 S. Micallef, Y. Couilard, P. G. C. Campbell, A. Tessier, Talanta, 39, 1073-1079 (1992)
4-26 M. A. Morcillo, J. Santamaria, J. Chromatogr., 655, 77 (1993)
4-27 D. E. Laurin, K. C. Klasing, R. L. Baldwin, Biochromatography, 4, 254 (1989)
4-28 S. G. Ang, V. W. T. Wong, J. Liq. Chromatogr., 14, 2647 (1991)
4-29 S. G. Ang, V. W. T. Wong, J. Chromatogr., 599, 21 (1992)
4-30 M. Nordberg, Y. Kojima, in:J. H. R. Kägi, M. Nordberg (Eds.), “Metallothionein and Other Low Molecular Weight Metal-Binding Proteins Metallothionein ”, Birkhauser, Basel, 41-116 (1979)
4-31 M. Nordberg, Talanta, 46, 243-254 (1998)
4-32 G. B. Irvine, Anal. Chem. Acta, 352, 387 (1997)
4-33 B. Gercken, R. M. Barnes, Anal. Chem., 63, 283-287 (1991)
4-34 K. T. Suzuki, Analusis Magazine, 26, N 6 (1998)
4-35 http://www.medicalvillage.org.tw/medbook/medician/4801.htm
4-36 http://www.mdschoice.com/elements/elements/trace_minerals/copper.htm
4-37 http://www.vghtpe.gov.tw/~biochem/SOP/Cu.htm
4-38 W. M. Becker, J. B. Reece, M. F. Poenie, The World of the Cell 3th, The Benjamin/Cummings Publishing Company (1996)
4-39 K. Pomazal, C. Prohaska, I. Steffan, G. Reich, J. F. K. Huber, Analyst, 124, 657-663 (1999)