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肌酸激酶 (Creatine Kinase, CK) (ATP: Creatine N-phosphotransferase EC 2.7.3.2)通常存在於動物的心臟、肌肉以及腦等組織的細胞漿和線粒體中,是一個與細胞內能量運轉、肌肉收縮、ATP再生有直接關係的重要激酶1,2,它可逆地催化肌酸與ATP之間的轉磷醯基反應。

1基本形式

中文名稱:血清磷酸肌酸激酶
肌酸激酶有四種同功酶形式:肌肉型(MM)、腦型(BB)、雜化型(MB)和線粒體型(MiMi)。MM型主要存在於各種肌肉細胞中,BB型主要存在於腦細胞中,MB型主要存在於心肌細胞中,MiMi型主要存在於心肌和骨骼肌線粒體中。肌肉型肌酸激酶分子是由兩個相同的亞基組成的二聚體。根據目前已經測定的兔、人、雞、鼠肌酸激酶的一級結構[3-6],M型亞基由387個氨基酸殘基組成,質量為43 KDa左右,分子內有8個巰基,但無二硫鍵。大熊貓肌肉型肌酸激酶也是二聚體酶,每個亞基由376個氨基酸殘基組成,分子量為42 KDa[7]。

2臨床價值

肌酸激酶的同功酶在臨床診斷中有十分重要的意義[2,8-10],在各種病變包括肌肉萎縮和心肌梗塞發生時,人的血清中肌酸激酶水平迅速提高,目前認為在心肌梗塞的診斷中測定肌酸激酶的活性比做心電圖更為可靠。心肌梗死時,肌酸激酶在起病6小時內升高,24小時達高峰,3-4日內恢復正常。其中肌酸激酶的同工酶CK-MB診斷的特異性最高。肌酸激酶因其具有重要的生理功能和臨床應用價值已引起人們廣泛的重視和深入的研究。

3實驗作用

肌酸激酶作為研究蛋白質摺疊的理想模型基於以下理由:i) 肌肉型肌酸激酶分子是由兩個相同的亞基組成的二聚體,目前兔肌CK的2.35 Å高解析度晶體結構已經解出[11],每個亞基具有一個小的N-末端結構域和一個大的C-末端結構域。人肌CK的3.5Å解析度晶體結構也已經得到[12]。ii)多種條件下變性或修飾后的CK在體外仍可再摺疊為天然構象[13-16]。iii). CK是一個大的二聚體蛋白質,比小的二聚體或單體蛋白質分子更複雜,再摺疊過程中可以得到更多的中間體[16-18],聚沉與正確摺疊之間的競爭也被觀察到[19,20]。
天然的肌酸激酶分子是一個緊密的球狀結構。近來關於肌酸激酶構象變化和活力變化關係的研究顯示了酶分子活性部位構象的柔性[17,21,22],即酶分子活性部位的微區構象在變性劑作用下易發生改變而導致酶分子快速失活,此時酶分子整體構象尚未發生明顯變化。周海夢等人[23]用熒光探針標記兔肌肌酸激酶的活性部位,監測了熒光衍生物微區構象變化與相應酶活力喪失速度,發現二者幾乎一致,為酶活性部位柔性的假說提供了有力的證據。

4參考文獻

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