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Ribbon diagram of glycosidase with an arrow showing the cleavage of the maltose sugar substrate into two glucose products.
葡糖苷酶英語Glucosidases能將一分子麥芽糖轉化爲兩分子葡萄糖。圖中活性位點以紅色表示,麥芽糖以黑色表示,輔酶NAD以黃色表示(PDB 1OBB

(Enzymes(英語發音:/ˈɛnzmz/ ))是一種大分子生物催化劑。酶能加快化學反應的速度(即具有催化作用)。由酶催化的反應中,反應物稱爲受質(substrates),生成的物質稱爲產物。幾乎所有細胞內的代謝過程都離不開酶。酶能大大加快這些過程中各化學反應進行的速率,使代謝產生的物質和能量能滿足生物體的需求[1]:8.1。細胞中酶的類型對可在該細胞中發生的代謝途徑的類型起決定作用。對酶進行研究的學科稱爲「酶學」(enzymology)。

目前已知酶可以催化超過5000種生化反應[2]。大部分酶是蛋白質,有少部分酶是具有催化活性的RNA分子(即核酶)。酶的特異性是由其獨特的三維結構決定的。

和所有的催化劑一樣,酶通過降低反應活化能加快化學反應的速率。一些酶可以將受質轉化爲產物的速率提高數百萬倍。一個比較極端的例子是乳清苷-5'-磷酸脫羧酶英語Orotidine 5'-phosphate decarboxylase。該酶可以使在無催化劑條件下需要進行數百萬年的化學反應在幾毫秒內完成[3][4]。從化學原理上講,酶和其它所有催化劑一樣,反應不會使其物質量發生變化。酶亦不能改變化學反應的平衡,這一點和其它催化劑也是一樣的。酶和其它催化劑的不同之處在於,它們的專一性要強得多。一些分子可以影響酶的活性。如酶抑制劑能降低酶的活性,酶活化劑能提高酶的活性。許多藥物毒物是酶的抑制劑。當超出適宜的溫度pH值後,酶的活性會顯著下降。

一些酶業已投入商用。抗生素的合成即是一例。一些家用產品也使用酶來提高化學反應的速率:洗衣粉中添加酶能加速附著在衣物上的蛋白質、澱粉或脂肪漬的分解,嫩肉粉中加入能將蛋白質分解爲稍小的分子,使肉的口感更嫩滑。

詞源和歷史[編輯]

結構[編輯]

Lysozyme displayed as an opaque globular surface with a pronounced cleft which the substrate depicted as a stick diagram snuggly fits into
酶結構的組織(以溶菌酶爲例)。圖中結合位點以藍色表示,催化位點以紅色表示,受質肽聚糖以黑色表示(PDB 9LYZ
A graph showing that reaction rate increases exponentially with temperature until denaturation causes it to decrease again.
酶活性最初隨溫度升高而增加(Q10爲正),直到酶的結構開始去摺疊化(即變性)。因而酶促反應的速度在適中的溫度條件下是最快的

酶大都是球蛋白,以單體或聚成複合物對反應進行催化。和其他的蛋白質一樣,酶的三維結構是通過多肽鏈摺疊形成的。胺基酸的序列(一級結構)能決定蛋白質的三維結構,進而影響酶的催化活性[18]。儘管結構決定功能是一條具普適性的規則,一種新的酶的活性不能僅僅通過其結構預測[19]。加熱時或與化學變性劑接觸時,酶結構會發生去摺疊(即變性),原有的結構被打亂,活性也往往隨之喪失[20]。在溫度超過正常水平時,酶就會變性。因此,不難推斷生活在火山環境(比如熱泉)中的細菌的酶具有很強的耐熱性。這些酶使高溫條件下酶促反應的發生成爲可能,在工業上具有很高的利用價值。

酶通常比受質大得多。酶的肽鏈長度從62個胺基酸殘基的4-草醯巴豆酸異構酶英語4-Oxalocrotonate tautomerase單體[21]到長度超過2,500個胺基酸殘基的動物脂肪酸合酶[22]。酶的結構只有一小部分(大約2-4個胺基酸)是直接與催化相關的。這部分稱爲催化位點(catalytic site)[23]。催化位點通常與一個或多個與受質結合的結合位點英語Binding site(binding site)相連。催化位點與結合位點共同組成了酶的活性位點(active site)。酶的其餘部分起維持活性位點準確的方向以及動力學特性的作用[24]

在一些酶中,催化與任何一個胺基酸都沒有關係。這類酶另有與催化輔助因子結合的位點[24]。一些酶亦可能包含異位位點。小分子與異位位點的結合可使酶發生構象改變,進而使酶的活性降低或升高[25]

一些具有生物催化活性的RNA分子稱爲核酶(ribozyme)。這類分子可能單獨發揮催化作用,也可能在與蛋白質結合成複合物的條件下發揮催化作用。最常見的核酶應是核糖體。核糖體是蛋白質以及具有催化活性的RNA的複合物。核糖體的活性位點完全由RNA組成,而蛋白質僅起支架的作用[1]:2.2[26]:695-701

機制[編輯]

受質結合[編輯]

酶在催化化學反應前必須要與受質結合。酶具有很強的專一性,通常僅能與寥寥數種受質結合,催化一種或幾種反應。專一性通過結合區的形狀、電荷、疏水/親水性與受質互補實現。因此,酶可以用來區分化學選擇性英語chemoselectivity上、區域選擇性上、立體專一性上有所不同的結構相似的分子[27]

一些與基因組複製表達相關的酶具有很高的專一性和準確性。一些酶有校對機制。以DNA聚合酶爲例,這類酶先催化DNA鏈的合成,再檢查新加上的鹼基是否正確[28]。校對機制確保了酶的極高準確性,哺乳動物的高保真DNA聚合酶在每一億次反應中才會出一次錯誤[1]:5.3.1。RNA聚合酶、氨醯-tRNA合成酶[29]核糖體[30]也有與DNA聚合酶類似的校對機制[31]

另外,一些酶表現出酶亂交英語enzyme promiscuity(enzyme promiscuity)的現象。這類酶專一性弱,能與一系列生理上相關的受質反應。一些酶偶爾會出現數值不高的副反應活性(即中性進化)。這樣的變化可能會成爲酶的新功能的進化起點[32][33]

Hexokinase displayed as an opaque surface with a pronounced open binding cleft next to unbound substrate (top) and the same enzyme with more closed cleft that surrounds the bound substrate (bottom)
在與受質發生誘導契合後,酶改變形狀,生成酶—受質複合物。己糖激酶的誘導契合運動較大,能包覆住受質ATP木糖。圖中結合位點用藍色表示,受質用黑色表示,Mg2+輔助因子用黃色表示(PDB 2E2N, 2E2Q

「鑰匙和鎖」模型[編輯]

爲了解釋觀察到的酶的特異性,1894年,赫爾曼·埃米爾·費歇爾提出,酶和受質靠著互補的幾何形狀精準地結合在一起[34]。這一理論即通常所說的「鑰匙和鎖」模型[1]:8.3.2。這一早期的理論解釋了酶的專一性,但卻沒能解釋酶的過渡態爲何能穩定存在[35]

誘導契合模型[編輯]

1958年,丹尼爾·科甚蘭英語Daniel E. Koshland, Jr.提出了一個對鑰匙與鎖模型進行修正的理論:酶的結構相對靈活,受質與酶(活性位點)作用時,活性位點會不斷改變結構[36]。受質不是簡單地與一個剛性的活性位點結合。組成活性位點的胺基酸側鏈的準確有序排布保證酶能執行催化功能。糖苷酶等酶,當受質分子與活性位點結合時,受質分子亦會發生輕微的形狀改變[37]。直到受質與酶發生完全結合,分子形狀和電荷排布都最終確定,活性位點都會不斷發生結構變化[38]誘導契合可以通過結構校對英語Conformational proofreading(conformational proofreading)機制在噪音和競爭物存在的條件下增強分子識別的保真度[39]

催化作用[編輯]

酶可以通過多種途徑加快化學反應的進行速度。這些途徑的機理是降低反應活化能(ΔG吉布斯自由能[40]

  1. 通過使過度態更加穩定:
    • 產生一個與過度態(物質)所帶電荷互補的環境,以降低其能量[41]
  2. 提供一條不同的反應途徑:
    • 先和受質發生反應,與受質通過共價鍵結合,形成一個能量較低的中間體[42]
  3. 使處於基態的受質穩定性降低:
    • 通過耗能較低的途徑將受質轉化為過渡態[43]
    • 通過改變受質的排列方式,減少反應的[44] The contribution of this mechanism to catalysis is relatively small.[45]

酶可能會同時使用多種途徑催化化學反應。比如胰蛋白酶(trypsin)通過一個催化三聯體催化化學反應,藉助氧負離子洞英語oxyanion hole(oxyanion hole)改變過渡態的電荷排布,達到增強過渡態穩定性的作用,水解過程的完成則依賴排布有序的水分子。

動力學[編輯]

各行業的應用[編輯]

酶因爲能高效催化特定反應,已在化工等行業得到廣泛應用。總的來說,酶的應用因爲它們能催化的反應數目少、在有機溶劑中以及高溫環境下不穩定而受到限制。因此,酶工程這一熱門學科應運而生。酶工程旨在藉助合理的設計或體外進化的方法研發具有新特性的酶[95][96]。目前,酶工程學已取得了一定成果,研究人員甚至已「從頭」(即不以任何自然界中的酶爲模板)設計出了一些能催化在自然界中不能發生的反應的酶[97]

參見[編輯]

參考[編輯]

  1. ^ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 Stryer L, Berg JM, Tymoczko JL. Biochemistry 5th. San Francisco: W.H. Freeman. 2002. ISBN 0-7167-4955-6. 開放獲取內容
  2. ^ Schomburg I, Chang A, Placzek S, Söhngen C, Rother M, Lang M, Munaretto C, Ulas S, Stelzer M, Grote A, Scheer M, Schomburg D. BRENDA in 2013: integrated reactions, kinetic data, enzyme function data, improved disease classification: new options and contents in BRENDA. Nucleic Acids Research. January 2013, 41 (Database issue): D764–72. doi:10.1093/nar/gks1049. PMC 3531171. PMID 23203881. 
  3. ^ Radzicka A, Wolfenden R. A proficient enzyme. Science. January 1995, 267 (5194): 90–931. Bibcode:1995Sci...267...90R. doi:10.1126/science.7809611. PMID 7809611. 
  4. ^ Callahan BP, Miller BG. OMP decarboxylase—An enigma persists. Bioorganic Chemistry. December 2007, 35 (6): 465–9. doi:10.1016/j.bioorg.2007.07.004. PMID 17889251. 
  5. ^ de Réaumur RA. Observations sur la digestion des oiseaux. Histoire de l'academie royale des sciences. 1752, 1752: 266, 461. 
  6. ^ Williams HS. A History of Science: in Five Volumes. Volume IV: Modern Development of the Chemical and Biological Sciences. Harper and Brothers. 1904. 
  7. ^ Payen A, Persoz JF. Mémoire sur la diastase, les principaux produits de ses réactions et leurs applications aux arts industriels [Memoir on diastase, the principal products of its reactions, and their applications to the industrial arts]. Annales de chimie et de physique. 2nd. 1833, 53: 73–92 (French). 
  8. ^ Manchester KL. Louis Pasteur (1822–1895)–chance and the prepared mind. Trends in Biotechnology. December 1995, 13 (12): 511–5. doi:10.1016/S0167-7799(00)89014-9. PMID 8595136. 
  9. ^ Kühne coined the word "enzyme" in: Kühne W. Über das Verhalten verschiedener organisirter und sog. ungeformter Fermente [On the behavior of various organized and so-called unformed ferments]. Verhandlungen des naturhistorisch-medicinischen Vereins zu Heidelberg. new series. 1877, 1 (3): 190–193 (German).  The relevant passage occurs on page 190: "Um Missverständnissen vorzubeugen und lästige Umschreibungen zu vermeiden schlägt Vortragender vor, die ungeformten oder nicht organisirten Fermente, deren Wirkung ohne Anwesenheit von Organismen und ausserhalb derselben erfolgen kann, als Enzyme zu bezeichnen." (Translation: In order to obviate misunderstandings and avoid cumbersome periphrases, [the author, a university lecturer] suggests designating as "enzymes" the unformed or not organized ferments, whose action can occur without the presence of organisms and outside of the same.)
  10. ^ Holmes FL. Enzymes. (編) Heilbron JL. The Oxford Companion to the History of Modern Science. Oxford: Oxford University Press. 2003: 270. 
  11. ^ Eduard Buchner. Nobel Laureate Biography. Nobelprize.org. [23 February 2015]. 
  12. ^ Eduard Buchner – Nobel Lecture: Cell-Free Fermentation. Nobelprize.org. 1907 [23 February 2015]. 
  13. ^ The naming of enzymes by adding the suffix "-ase" to the substrate on which the enzyme acts, has been traced to French scientist Émile Duclaux (1840–1904), who intended to honor the discoverers of diastase – the first enzyme to be isolated – by introducing this practice in his book Duclaux E. Traité de microbiologie: Diastases, toxines et venins [Microbiology Treatise: diastases , toxins and venoms]. Paris, France: Masson and Co. 1899 (French).  See Chapter 1, especially page 9.
  14. ^ Willstätter R. Faraday lecture. Problems and methods in enzyme research. Journal of the Chemical Society (Resumed). 1927: 1359. doi:10.1039/JR9270001359.  quoted in Blow D. So do we understand how enzymes work? (pdf). Structure (London, England : 1993). April 2000, 8 (4): R77–R81. doi:10.1016/S0969-2126(00)00125-8. PMID 10801479. 
  15. ^ Nobel Prizes and Laureates: The Nobel Prize in Chemistry 1946. Nobelprize.org. [23 February 2015]. 
  16. ^ Blake CC, Koenig DF, Mair GA, North AC, Phillips DC, Sarma VR. Structure of hen egg-white lysozyme. A three-dimensional Fourier synthesis at 2 Ångström resolution. Nature. May 1965, 206 (4986): 757–61. Bibcode:1965Natur.206..757B. doi:10.1038/206757a0. PMID 5891407. 
  17. ^ Johnson LN, Petsko GA. David Phillips and the origin of structural enzymology. Trends Biochem. Sci. 1999, 24 (7): 287–9. doi:10.1016/S0968-0004(99)01423-1. PMID 10390620. 
  18. ^ Anfinsen CB. Principles that govern the folding of protein chains. Science. July 1973, 181 (4096): 223–30. Bibcode:1973Sci...181..223A. doi:10.1126/science.181.4096.223. PMID 4124164. 
  19. ^ Dunaway-Mariano D. Enzyme function discovery. Structure (London, England : 1993). November 2008, 16 (11): 1599–600. doi:10.1016/j.str.2008.10.001. PMID 19000810. 
  20. ^ Petsko GA, Ringe D. Chapter 1: From sequence to structure. Protein structure and function. London: New Science. 2003: 27. ISBN 978-1405119221. 
  21. ^ Chen LH, Kenyon GL, Curtin F, Harayama S, Bembenek ME, Hajipour G, Whitman CP. 4-Oxalocrotonate tautomerase, an enzyme composed of 62 amino acid residues per monomer. The Journal of Biological Chemistry. September 1992, 267 (25): 17716–21. PMID 1339435. 
  22. ^ Smith S. The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. FASEB Journal. December 1994, 8 (15): 1248–59. PMID 8001737. 
  23. ^ The Catalytic Site Atlas. The European Bioinformatics Institute. [4 April 2007]. 
  24. ^ 24.0 24.1 Suzuki H. Chapter 7: Active Site Structure. How Enzymes Work: From Structure to Function. Boca Raton, FL: CRC Press. 2015: 117–140. ISBN 978-981-4463-92-8. 
  25. ^ Krauss G. The Regulations of Enzyme Activity. Biochemistry of Signal Transduction and Regulation 3rd. Weinheim: Wiley-VCH. 2003: 89–114. ISBN 9783527605767. 
  26. ^ Jocelyn E.KREBS; 等. Gene XI. JONES&BARTLETT LEARNING(高等教育出版社出版). 2014. ISBN 978-7-04-039649-2. 
  27. ^ Jaeger KE, Eggert T. Enantioselective biocatalysis optimized by directed evolution. Current Opinion in Biotechnology. August 2004, 15 (4): 305–13. doi:10.1016/j.copbio.2004.06.007. PMID 15358000. 
  28. ^ Shevelev IV, Hübscher U. The 3' 5' exonucleases. Nature Reviews Molecular Cell Biology. May 2002, 3 (5): 364–76. doi:10.1038/nrm804. PMID 11988770. 
  29. ^ Ibba M, Soll D. Aminoacyl-tRNA synthesis. Annual Review of Biochemistry. 2000, 69: 617–50. doi:10.1146/annurev.biochem.69.1.617. PMID 10966471. 
  30. ^ Rodnina MV, Wintermeyer W. Fidelity of aminoacyl-tRNA selection on the ribosome: kinetic and structural mechanisms. Annual Review of Biochemistry. 2001, 70: 415–35. doi:10.1146/annurev.biochem.70.1.415. PMID 11395413. 
  31. ^ Zenkin N, Yuzenkova Y, Severinov K. Transcript-assisted transcriptional proofreading. Science. July 2006, 313 (5786): 518–20. Bibcode:2006Sci...313..518Z. doi:10.1126/science.1127422. PMID 16873663. 
  32. ^ Khersonsky O, Tawfik DS. Enzyme promiscuity: a mechanistic and evolutionary perspective. Annual Review of Biochemistry. 2010, 79: 471–505. doi:10.1146/annurev-biochem-030409-143718. PMID 20235827. 
  33. ^ O'Brien PJ, Herschlag D. Catalytic promiscuity and the evolution of new enzymatic activities. Chemistry & Biology. April 1999, 6 (4): R91–R105. doi:10.1016/S1074-5521(99)80033-7. PMID 10099128. 
  34. ^ Fischer E. Einfluss der Configuration auf die Wirkung der Enzyme [Influence of configuration on the action of enzymes]. Berichte der Deutschen chemischen Gesellschaft zu Berlin. 1894, 27 (3): 2985–93. doi:10.1002/cber.18940270364 (German).  From page 2992: "Um ein Bild zu gebrauchen, will ich sagen, dass Enzym und Glucosid wie Schloss und Schlüssel zu einander passen müssen, um eine chemische Wirkung auf einander ausüben zu können." (To use an image, I will say that an enzyme and a glucoside [i.e., glucose derivative] must fit like a lock and key, in order to be able to exert a chemical effect on each other.)
  35. ^ Cooper GM. Chapter 2.2: The Central Role of Enzymes as Biological Catalysts. The Cell: a Molecular Approach 2nd. Washington (DC ): ASM Press. 2000. ISBN 0-87893-106-6. 
  36. ^ Koshland DE. Application of a Theory of Enzyme Specificity to Protein Synthesis. Proceedings of the National Academy of Sciences of the United States of America. February 1958, 44 (2): 98–104. Bibcode:1958PNAS...44...98K. doi:10.1073/pnas.44.2.98. PMC 335371. PMID 16590179. 
  37. ^ Vasella A, Davies GJ, Böhm M. Glycosidase mechanisms. Current Opinion in Chemical Biology. October 2002, 6 (5): 619–29. doi:10.1016/S1367-5931(02)00380-0. PMID 12413546. 
  38. ^ Boyer R. Chapter 6: Enzymes I, Reactions, Kinetics, and Inhibition. Concepts in Biochemistry 2nd. New York, Chichester, Weinheim, Brisbane, Singapore, Toronto.: John Wiley & Sons, Inc. 2002: 137–8. ISBN 0-470-00379-0. OCLC 51720783. 
  39. ^ Savir Y, Tlusty T. Scalas E, 編. Conformational proofreading: the impact of conformational changes on the specificity of molecular recognition (PDF). PLoS ONE. 2007, 2 (5): e468. Bibcode:2007PLoSO...2..468S. doi:10.1371/journal.pone.0000468. PMC 1868595. PMID 17520027. 
  40. ^ Fersht A. Enzyme Structure and Mechanism. San Francisco: W.H. Freeman. 1985: 50–2. ISBN 0-7167-1615-1. 
  41. ^ Warshel A, Sharma PK, Kato M, Xiang Y, Liu H, Olsson MH. Electrostatic basis for enzyme catalysis. Chemical Reviews. August 2006, 106 (8): 3210–35. doi:10.1021/cr0503106. PMID 16895325. 
  42. ^ Cox MM, Nelson DL. Chapter 6.2: How enzymes work. Lehninger Principles of Biochemistry 6th. New York, N.Y.: W.H. Freeman. 2013: 195. ISBN 978-1464109621. 
  43. ^ Benkovic SJ, Hammes-Schiffer S. A perspective on enzyme catalysis. Science. August 2003, 301 (5637): 1196–202. Bibcode:2003Sci...301.1196B. doi:10.1126/science.1085515. PMID 12947189. 
  44. ^ Jencks WP. Catalysis in Chemistry and Enzymology. Mineola, N.Y: Dover. 1987. ISBN 0-486-65460-5. 
  45. ^ Villa J, Strajbl M, Glennon TM, Sham YY, Chu ZT, Warshel A. How important are entropic contributions to enzyme catalysis?. Proceedings of the National Academy of Sciences of the United States of America. October 2000, 97 (22): 11899–904. Bibcode:2000PNAS...9711899V. doi:10.1073/pnas.97.22.11899. PMC 17266. PMID 11050223. 
  46. ^ Ramanathan A, Savol A, Burger V, Chennubhotla CS, Agarwal PK. Protein conformational populations and functionally relevant substates. Acc. Chem. Res. 2014, 47 (1): 149–56. doi:10.1021/ar400084s. PMID 23988159. 
  47. ^ Tsai CJ, Del Sol A, Nussinov R. Protein allostery, signal transmission and dynamics: a classification scheme of allosteric mechanisms. Mol Biosyst. 2009, 5 (3): 207–16. doi:10.1039/b819720b. PMC 2898650. PMID 19225609. 
  48. ^ Changeux JP, Edelstein SJ. Allosteric mechanisms of signal transduction. Science. June 2005, 308 (5727): 1424–8. Bibcode:2005Sci...308.1424C. doi:10.1126/science.1108595. PMID 15933191. 
  49. ^ de Bolster MW. Glossary of Terms Used in Bioinorganic Chemistry: Cofactor. International Union of Pure and Applied Chemistry. 1997 [30 October 2007]. 
  50. ^ Chapman-Smith A, Cronan JE. The enzymatic biotinylation of proteins: a post-translational modification of exceptional specificity. Trends Biochem. Sci. 1999, 24 (9): 359–63. doi:10.1016/s0968-0004(99)01438-3. PMID 10470036. 
  51. ^ Fisher Z, Hernandez Prada JA, Tu C, Duda D, Yoshioka C, An H, Govindasamy L, Silverman DN, McKenna R. Structural and kinetic characterization of active-site histidine as a proton shuttle in catalysis by human carbonic anhydrase II. Biochemistry. February 2005, 44 (4): 1097–115. doi:10.1021/bi0480279. PMID 15667203. 
  52. ^ 52.0 52.1 Wagner AL. Vitamins and Coenzymes. Krieger Pub Co. 1975. ISBN 0-88275-258-8. 
  53. ^ BRENDA The Comprehensive Enzyme Information System. Technische Universität Braunschweig. [23 February 2015]. 
  54. ^ Törnroth-Horsefield S, Neutze R. Opening and closing the metabolite gate. Proceedings of the National Academy of Sciences of the United States of America. December 2008, 105 (50): 19565–6. Bibcode:2008PNAS..10519565T. doi:10.1073/pnas.0810654106. PMC 2604989. PMID 19073922. 
  55. ^ McArdle WD, Katch F, Katch VL. Chapter 9: The Pulmonary System and Exercise. Essentials of Exercise Physiology 3rd. Baltimore, Maryland: Lippincott Williams & Wilkins. 2006: 312–3. ISBN 978-0781749916. 
  56. ^ Ferguson SJ, Nicholls D, Ferguson S. Bioenergetics 3 3rd. San Diego: Academic. 2002. ISBN 0-12-518121-3. 
  57. ^ Michaelis L, Menten M. Die Kinetik der Invertinwirkung [The Kinetics of Invertase Action]. Biochem. Z. 1913, 49: 333–369 (German).  ; Michaelis L, Menten ML, Johnson KA, Goody RS. The original Michaelis constant: translation of the 1913 Michaelis-Menten paper. Biochemistry. 2011, 50 (39): 8264–9. doi:10.1021/bi201284u. PMC 3381512. PMID 21888353. 
  58. ^ Briggs GE, Haldane JB. A Note on the Kinetics of Enzyme Action. The Biochemical Journal. 1925, 19 (2): 339–339. doi:10.1042/bj0190338. PMC 1259181. PMID 16743508. 
  59. ^ Ellis RJ. Macromolecular crowding: obvious but underappreciated. Trends in Biochemical Sciences. October 2001, 26 (10): 597–604. doi:10.1016/S0968-0004(01)01938-7. PMID 11590012. 
  60. ^ Kopelman R. Fractal reaction kinetics. Science. September 1988, 241 (4873): 1620–26. Bibcode:1988Sci...241.1620K. doi:10.1126/science.241.4873.1620. PMID 17820893. 
  61. ^ 61.0 61.1 61.2 61.3 Cornish-Bowden A. Fundamentals of Enzyme Kinetics 3. London: Portland Press. 2004. ISBN 1-85578-158-1. 
  62. ^ Price NC. What is meant by 'competitive inhibition'?. Trends in Biochemical Sciences. 1979, 4 (11): N272–N273. doi:10.1016/0968-0004(79)90205-6. 
  63. ^ Cornish-Bowden A. Why is uncompetitive inhibition so rare? A possible explanation, with implications for the design of drugs and pesticides. FEBS Letters. July 1986, 203 (1): 3–6. doi:10.1016/0014-5793(86)81424-7. PMID 3720956. 
  64. ^ Fisher JF, Meroueh SO, Mobashery S. Bacterial resistance to beta-lactam antibiotics: compelling opportunism, compelling opportunity. Chemical Reviews. February 2005, 105 (2): 395–424. doi:10.1021/cr030102i. PMID 15700950. 
  65. ^ 65.0 65.1 Johnson DS, Weerapana E, Cravatt BF. Strategies for discovering and derisking covalent, irreversible enzyme inhibitors. Future Medicinal Chemistry. June 2010, 2 (6): 949–64. doi:10.4155/fmc.10.21. PMC 2904065. PMID 20640225. 
  66. ^ Endo A. The discovery and development of HMG-CoA reductase inhibitors (PDF). J. Lipid Res. 1 November 1992, 33 (11): 1569–82. PMID 1464741. 
  67. ^ Wlodawer A, Vondrasek J. Inhibitors of HIV-1 protease: a major success of structure-assisted drug design. Annual Review of Biophysics and Biomolecular Structure. 1998, 27: 249–84. doi:10.1146/annurev.biophys.27.1.249. PMID 9646869. 
  68. ^ Yoshikawa S, Caughey WS. Infrared evidence of cyanide binding to iron and copper sites in bovine heart cytochrome c oxidase. Implications regarding oxygen reduction. The Journal of Biological Chemistry. May 1990, 265 (14): 7945–58. PMID 2159465. 
  69. ^ Hunter T. Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell. January 1995, 80 (2): 225–36. doi:10.1016/0092-8674(95)90405-0. PMID 7834742. 
  70. ^ Berg JS, Powell BC, Cheney RE. A millennial myosin census. Molecular Biology of the Cell. April 2001, 12 (4): 780–94. doi:10.1091/mbc.12.4.780. PMC 32266. PMID 11294886. 
  71. ^ Meighen EA. Molecular biology of bacterial bioluminescence. Microbiological Reviews. March 1991, 55 (1): 123–42. PMC 372803. PMID 2030669. 
  72. ^ De Clercq E. Highlights in the development of new antiviral agents. Mini Rev Med Chem. 2002, 2 (2): 163–75. doi:10.2174/1389557024605474. PMID 12370077. 
  73. ^ Mackie RI, White BA. Recent advances in rumen microbial ecology and metabolism: potential impact on nutrient output. Journal of Dairy Science. October 1990, 73 (10): 2971–95. doi:10.3168/jds.S0022-0302(90)78986-2. PMID 2178174. 
  74. ^ Rouzer CA, Marnett LJ. Cyclooxygenases: structural and functional insights. J. Lipid Res. 2009,. 50 Suppl: S29–34. doi:10.1194/jlr.R800042-JLR200. PMC 2674713. PMID 18952571. 
  75. ^ 75.0 75.1 75.2 75.3 Suzuki H. Chapter 8: Control of Enzyme Activity. How Enzymes Work: From Structure to Function. Boca Raton, FL: CRC Press. 2015: 141–69. ISBN 978-981-4463-92-8. 
  76. ^ Doble BW, Woodgett JR. GSK-3: tricks of the trade for a multi-tasking kinase. Journal of Cell Science. April 2003, 116 (Pt 7): 1175–86. doi:10.1242/jcs.00384. PMC 3006448. PMID 12615961. 
  77. ^ Bennett PM, Chopra I. Molecular basis of beta-lactamase induction in bacteria (PDF). Antimicrob. Agents Chemother. 1993, 37 (2): 153–8. doi:10.1128/aac.37.2.153. PMC 187630. PMID 8452343. 
  78. ^ Skett P, Gibson GG. Chapter 3: Induction and Inhibition of Drug Metabolism. Introduction to Drug Metabolism 3. Cheltenham, UK: Nelson Thornes Publishers. 2001: 87–118. ISBN 978-0748760114. 
  79. ^ Faergeman NJ, Knudsen J. Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling. The Biochemical Journal. April 1997, 323 (Pt 1): 1–12. PMC 1218279. PMID 9173866. 
  80. ^ Suzuki H. Chapter 4: Effect of pH, Temperature, and High Pressure on Enzymatic Activity. How Enzymes Work: From Structure to Function. Boca Raton, FL: CRC Press. 2015: 53–74. ISBN 978-981-4463-92-8. 
  81. ^ Kamata K, Mitsuya M, Nishimura T, Eiki J, Nagata Y. Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase. Structure. March 2004, 12 (3): 429–38. doi:10.1016/j.str.2004.02.005. PMID 15016359. 
  82. ^ Froguel P, Zouali H, Vionnet N, Velho G, Vaxillaire M, Sun F, Lesage S, Stoffel M, Takeda J, Passa P. Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus. The New England Journal of Medicine. March 1993, 328 (10): 697–702. doi:10.1056/NEJM199303113281005. PMID 8433729. 
  83. ^ Okada S, O'Brien JS. Tay-Sachs disease: generalized absence of a beta-D-N-acetylhexosaminidase component. Science. August 1969, 165 (3894): 698–700. Bibcode:1969Sci...165..698O. doi:10.1126/science.165.3894.698. PMID 5793973. 
  84. ^ Learning About Tay-Sachs Disease. U.S. National Human Genome Research Institute. [1 March 2015]. 
  85. ^ Erlandsen H, Stevens RC. The structural basis of phenylketonuria. Molecular Genetics and Metabolism. October 1999, 68 (2): 103–25. doi:10.1006/mgme.1999.2922. PMID 10527663. 
  86. ^ Flatmark T, Stevens RC. Structural Insight into the Aromatic Amino Acid Hydroxylases and Their Disease-Related Mutant Forms. Chemical Reviews. August 1999, 99 (8): 2137–2160. doi:10.1021/cr980450y. PMID 11849022. 
  87. ^ Phenylketonuria. Genes and Disease [Internet]. Bethesda (MD): National Center for Biotechnology Information (US). 1998–2015. 
  88. ^ Pseudocholinesterase deficiency. U.S. National Library of Medicine. [5 September 2013]. 
  89. ^ Fieker A, Philpott J, Armand M. Enzyme replacement therapy for pancreatic insufficiency: present and future. Clinical and Experimental Gastroenterology. 2011, 4: 55–73. doi:10.2147/CEG.S17634. PMC 3132852. PMID 21753892. 
  90. ^ Misselwitz B, Pohl D, Frühauf H, Fried M, Vavricka SR, Fox M. Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment. United European Gastroenterology Journal. June 2013, 1 (3): 151–9. doi:10.1177/2050640613484463. PMC 4040760. PMID 24917953. 
  91. ^ Cleaver JE. Defective repair replication of DNA in xeroderma pigmentosum. Nature. May 1968, 218 (5142): 652–6. Bibcode:1968Natur.218..652C. doi:10.1038/218652a0. PMID 5655953. 
  92. ^ James WD, Elston D, Berger TG. Andrews' Diseases of the Skin: Clinical Dermatology 11th. London: Saunders/ Elsevier. 2011: 567. ISBN 978-1437703146. 
  93. ^ Nomenclature Committee. Classification and Nomenclature of Enzymes by the Reactions they Catalyse. International Union of Biochemistry and Molecular Biology (NC-IUBMB). School of Biological and Chemical Sciences, Queen Mary, University of London. 
  94. ^ Nomenclature Committee. EC 2.7.1.1. International Union of Biochemistry and Molecular Biology (NC-IUBMB). School of Biological and Chemical Sciences, Queen Mary, University of London. 
  95. ^ Renugopalakrishnan V, Garduño-Juárez R, Narasimhan G, Verma CS, Wei X, Li P. Rational design of thermally stable proteins: relevance to bionanotechnology. Journal of Nanoscience and Nanotechnology. November 2005, 5 (11): 1759–1767. doi:10.1166/jnn.2005.441. PMID 16433409. 
  96. ^ Hult K, Berglund P. Engineered enzymes for improved organic synthesis. Current Opinion in Biotechnology. August 2003, 14 (4): 395–400. doi:10.1016/S0958-1669(03)00095-8. PMID 12943848. 
  97. ^ Jiang L, Althoff EA, Clemente FR, Doyle L, Röthlisberger D, Zanghellini A, Gallaher JL, Betker JL, Tanaka F, Barbas CF, Hilvert D, Houk KN, Stoddard BL, Baker D. De novo computational design of retro-aldol enzymes. Science. March 2008, 319 (5868): 1387–91. Bibcode:2008Sci...319.1387J. doi:10.1126/science.1152692. PMC 3431203. PMID 18323453. 
  98. ^ 98.0 98.1 Sun Y, Cheng J. Hydrolysis of lignocellulosic materials for ethanol production: a review. Bioresource Technology. May 2002, 83 (1): 1–11. doi:10.1016/S0960-8524(01)00212-7. PMID 12058826. 
  99. ^ 99.0 99.1 Kirk O, Borchert TV, Fuglsang CC. Industrial enzyme applications. Current Opinion in Biotechnology. August 2002, 13 (4): 345–351. doi:10.1016/S0958-1669(02)00328-2. PMID 12323357. 
  100. ^ 100.0 100.1 100.2 Briggs DE. Malts and Malting 1st. London: Blackie Academic. 1998. ISBN 978-0412298004. 
  101. ^ Dulieu C, Moll M, Boudrant J, Poncelet D. Improved performances and control of beer fermentation using encapsulated alpha-acetolactate decarboxylase and modeling. Biotechnology Progress. 2000, 16 (6): 958–65. doi:10.1021/bp000128k. PMID 11101321. 
  102. ^ Tarté R. Ingredients in Meat Products Properties, Functionality and Applications. New York: Springer. 2008: 177. ISBN 978-0-387-71327-4. 
  103. ^ Chymosin – GMO Database. GMO Compass. European Union. 10 July 2010 [1 March 2015]. 
  104. ^ Molimard P, Spinnler HE. Review: Compounds Involved in the Flavor of Surface Mold-Ripened Cheeses: Origins and Properties. Journal of Dairy Science. February 1996, 79 (2): 169–184. doi:10.3168/jds.S0022-0302(96)76348-8. 
  105. ^ Guzmán-Maldonado H, Paredes-López O. Amylolytic enzymes and products derived from starch: a review. Critical Reviews in Food Science and Nutrition. September 1995, 35 (5): 373–403. doi:10.1080/10408399509527706. PMID 8573280. 
  106. ^ 106.0 106.1 Protease – GMO Database. GMO Compass. European Union. 10 July 2010 [28 February 2015]. 
  107. ^ Alkorta I, Garbisu C, Llama MJ, Serra JL. Industrial applications of pectic enzymes: a review. Process Biochemistry. January 1998, 33 (1): 21–28. doi:10.1016/S0032-9592(97)00046-0. 
  108. ^ Bajpai P. Application of enzymes in the pulp and paper industry. Biotechnology Progress. March 1999, 15 (2): 147–157. doi:10.1021/bp990013k. PMID 10194388. 
  109. ^ Begley CG, Paragina S, Sporn A. An analysis of contact lens enzyme cleaners. Journal of the American Optometric Association. March 1990, 61 (3): 190–4. PMID 2186082. 
  110. ^ Farris PL. Economic Growth and Organization of the U.S. Starch Industry. (編) BeMiller JN, Whistler RL. Starch Chemistry and Technology 3rd. London: Academic. 2009. ISBN 9780080926551. 

拓展閱讀[編輯]

總論

  • Berg JM, Tymoczko JL, Stryer L. Biochemistry 5th. New York, NY: W. H. Freeman. 2002. ISBN 0-7167-3051-0. , A biochemistry textbook available free online through NCBI Bookshelf.開放獲取內容

詞源與歷史

'酶結構及作用機理

  • Suzuki H. How Enzymes Work: From Structure to Function. Boca Raton, FL: CRC Press. 2015. ISBN 978-981-4463-92-8. 

動力學及抑制

  • Cornish-Bowden A. Fundamentals of Enzyme Kinetics 4th. Weinheim: Wiley-VCH. 2012. ISBN 978-3527330744. 

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