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Ribbon diagram of glycosidase with an arrow showing the cleavage of the maltose sugar substrate into two glucose products.
葡糖苷酶英语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(英语发音:/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,反應物稱爲底物(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。一些酶可以將底物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'-磷酸脫羧酶英语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,酶激活劑能提高酶的活性。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着在衣物上的蛋白質、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[编辑]

結構[编辑]

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,底物肽聚糖以黑色表示(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。氨基酸的序列(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。

酶通常比底物大得多。酶的肽鏈長度從62個氨基酸殘基的4-草酰巴豆酸異構酶英语4-Oxalocrotonate tautomerase單體[21]到長度超過2,500個氨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個氨基酸)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底物結合的結合位點英语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,催化與任何一個氨基酸都沒有關係。這類酶另有與催化輔助因子結合的位點[24]。一些酶亦可能包含變構位點。小分子與變構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[编辑]

底物結合[编辑]

酶在催化化學反應前必須要與底物結合。酶具有很強的專一性,通常僅能與寥寥數種底物結合,催化一種或幾種反應。專一性通過結合區的形狀、電荷、疏水/親水性與底物互補實現。因此,酶可以用來區分化學選擇性英语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、氨酰-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语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底物反應。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)
在與底物發生誘導契合後,酶改變形狀,生成酶—底物複合物。己糖激酶的誘導契合運動較大,能包覆住底物ATP木糖。圖中結合位點用藍色表示,底物用黑色表示,Mg2+輔助因子用黃色表示(PDB 2E2N, 2E2Q

「鑰匙和鎖」模型[编辑]

爲了解釋觀察到的酶的特異性,1894年,赫尔曼·埃米尔·费歇尔提出,酶和底物靠着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[编辑]

1958年,丹尼爾·科甚蘭英语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,底物與酶(活性位點)作用時,活性位點會不斷改變結構[36]。底物不是簡單地與一個剛性的活性位點結合。組成活性位點的氨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,當底物分子與活性位點結合時,底物分子亦會發生輕微的形狀改變[37]。直到底物與酶發生完全結合,分子形狀和電荷排佈都最終確定,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语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[编辑]

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:
    • 先和底物發生反應,與底物通過共價鍵結合,形成一個能量較低的中間體[42]
  3. 使處於基態的底物穩定性降低:
    • 通過耗能較低的途徑將底物轉化為過渡態[43]
    • 通過改變底物的排列方式,減少反應的[44],此一機制對催化的貢獻較小。[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,借助氧負離子洞英语oxyanion hole(oxyanion hole)改變過渡態的電荷排佈,達到增強過渡態穩定性的作用,水解過程的完成則依賴排佈有序的水分子。

動力學[编辑]

酶的結構並不是剛性、恆定不變的。酶的內部結構會發生複雜的動力學變化。酶的結構可能在反應過程中發生變化,單個氨基酸殘基、一個轉角英语turn (biochemistry)、一個二級結構單位,乃至整個結構域的位置都可能發生改變。酶內部結構的變化能使差異度不大、且能發生互變的結構之間在熱力學平衡狀態下發生构象系综英语conformational ensemble(conformational ensemble)。在系综狀態下,酶的每一結構狀態都可能與酶的功能的某一部分有關。舉例來說,二氢叶酸还原酶的不同構象就分別和底物結合、催化、輔助因子釋放、產物釋放相關[46]

别构调节[编辑]

別構中心是酶當中一個可以讓分子和酶結合的區域,別構中心不同於活性中心的。和別構中心結合的分子可以改變酶的構象或是酶的动力学特性,因此影響酶活性中心的反應速率[47]。因此別構反應可以使酶活化,也可使其不活化。酶和代謝路徑上游或是下游代謝物的別構作用會有反馈調整,用路徑上的通量英语Flux (metabolism)來調整酶的活性[48]

輔助因子[编辑]

Thiamine pyrophosphate displayed as an opaque globular surface with an open binding cleft where the substrate and cofactor both depicted as stick diagrams fit into.
轉酮酶英语Transketolase(Transketolase)以及硫胺素焦磷酸的結構。黃色部分代表硫胺素焦磷酸,黑色部分代表木酮糖-5-磷酸PDB 4KXV

一些酶並不需要額外的組分就能就能正常發揮作用,另外一些酶則要在和輔助因子(cofactor)結合後才能顯示出活性[49]。輔助因子可以是無機物(如金屬離子铁硫簇),也可以是有機物(比如黃素血紅素)。有機輔助 因子如果在反應中會與酶分離則爲輔酶(coenzyme),如果與酶緊密結合則爲輔基(prosthetic groups)。有機的輔基可能與酶發生共價結合(丙酮酸羧化酶生物素(biotin)之間即發生共價結合)[50]

碳酸酐酶英语carbonic anhydrase(carbonic anhydrase)即是一類含有輔助因子的酶。理查德森圖英语ribbon diagram(ribbon diagram)顯示,碳酸酐酶的肽鏈環繞在一個鋅離子(值得注意的是,鋅離子亦是活性位點的一部分)周圍,並與這個鋅離子結合在一起[51]這些與酶緊密結合的離子或分子通常位於活性位點之中,並且能夠參與催化反應[1]:8.1.1。例如,黃素以及血紅素即會參與氧化還原反應[1]:17

需要輔助因子才可以發揮作用的酶,處於未與輔助因子狀態時稱爲「脫輔酶」(apoenzymesapoproteins),當其與輔助因子結合後則稱爲「全酶」(holoenzyme)。不過,值得注意的是,名詞全酶亦可以指含有多個亞基的酶,如DNA聚合酶。不過,在本文中,全酶是指含有所有發揮活性所需的亞基的酶[1]:8.1.1

輔酶[编辑]

輔酶是一類與酶結合的小分子有機物,輔酶與酶結合的強度因輔酶和酶的種類而異,或強或弱。輔酶能夠將化學基團從一個酶轉移到另一個酶上[52]NADHNADPH爲兩種常見的輔酶。核黃素硫胺葉酸維生素類輔酶人體不能合成,需要通過膳食補充。輔酶能攜帶化學基團,如NAD或NADP能攜帶離子(H+)、ATP能攜帶磷酸基團、輔酶A能攜帶乙酰基團、葉酸基團能攜帶甲酰基、次甲基,或甲基、S-腺苷甲硫氨酸能攜帶甲基[52]

輔酶在酶促反應發生後化學結構會發生改變。因此,可以將看作一類普遍存在的特殊底物。許多酶都有與之匹配的輔酶,比如,已知的酶中有大約1000種酶使用NADH作爲輔酶(2015年的數據)[53]

輔酶通常能不斷再生,濃度能始終維持在一個恆定不變的水平上。舉例來說,NADPH能通過磷酸戊糖途径再生,S-腺苷甲硫氨酸能通過甲硫氨酸腺苷轉移酶催化的反應生成。持續不斷的再生意味着總量不多的輔酶也能以很快的速度消耗。舉例來說,人類每天會更新重量與自身體重相等的ATP[54]

Thermodynamics[编辑]

Kinetics[编辑]

Inhibition[编辑]

Biological function[编辑]

命名規則[编辑]

酶的命名是衍生自其受質或是要催化的化學反,在字尾會加上-ase[1]:8.1.3。例如乳糖酶(lactase)、醇脫氫酶(alcohol dehydrogenase)及DNA聚合酶(DNA polymerase)。但有些化學反應可以由幾種不同的酶催化,這些酶稱為同工酶[1]:10.3,而上述的命名法無法處理同工酶的情形。

國際生物化學與分子生物學聯盟英语International Union of Biochemistry and Molecular Biology提出了酶的命名法英语nomenclature,也就是EC編號。每一個酶用一個四位數的數字表示,前面再加上"EC"。第一位數字是酶依酶促反應的機制來分類[93]

依照第一位數字,可以分為以下六類:

上述分類會再依底物、生成物及化學結構來分類。用四位數字可以完整的描述一個酶。例如,己糖激酶(EC 2.7.1.1)是轉移酶(EC 2),會將磷酸基團(EC 7)加到六碳糖中,是一個含有醇基的分子(EC 2.7.1)[94]

各行業的應用[编辑]

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]

應用領域 用途
生物燃料工業 纖維素酶 將纖維素分解可通過發酵轉化爲纖維素乙醇的糖[98]
木質酶英语Lignin-modifying enzyme 對準備用於生物燃料生產的生物質進行預處理[98]
生物洗滌劑英语Biological detergent 蛋白酶澱粉酶脂肪酶 洗衣或清洗餐具時去除蛋白質、澱粉、脂肪或油漬[99]
甘露聚糖酶英语Mannanase 去除食物食品污渍[99]
酿酒業 淀粉酶葡聚糖酶英语glucanase蛋白酶 麦芽中分解多醣及蛋白質[100]:150–9
β-葡聚醣酶英语Betaglucanase 提高麦汁英语wort和啤酒过滤特征[100]:545
淀粉葡糖苷酶支链淀粉酶英语pullulanase 製作低熱量啤酒及调整发酵特性[100]:575
乙酰乳酸脫羧酶英语Acetolactate decarboxylase(ALDC) 利用減少丁二酮形成來提昇发酵效率[101]
烹饪用 木瓜蛋白酶 使肉變嫰,容易烹饪[102]
乳品業 凝乳酶 奶酪生产過程中酸化蛋白质[103]
脂酶 製作卡芒贝尔奶酪及像罗克福干酪之類的藍乾酪[104]
食品加工 淀粉酶 淀粉製造糖類,例如製作高果糖玉米糖浆[105]
蛋白酶 降低面粉中的蛋白質比例,例如用在餅乾製造中[106]
胰蛋白酶 製作防过敏英语hypoallergenic的嬰兒食品[106]
纤维素酶果胶酶英语pectinase 澄清果汁[107]
分子生物學 核酸酶聚合酶DNA連接酶 藉助限制性核酸內切酶以及PCR技術產生重組DNA[1]:6.2
造紙業 木聚糖酶半纤维素酶木质素过氧化物酶英语lignin peroxidase 木浆中移除木质素[108]
个人护理英语Personal care 蛋白酶 清除隱形眼鏡上的蛋白質,防止感染。[109]
澱粉工業 淀粉酶 淀粉轉換成葡萄糖及各種糖漿[110]

參見[编辑]

參考[编辑]

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拓展閱讀[编辑]

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.开放获取内容

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.