van Deursen J, Jap P, Heerschap A, ter Laak H, Ruitenbeek W, Wieringa B
Department of Cell Biology and Histology, Faculty of Medical Sciences, University of Nijmegen, The Netherlands.
Biochim Biophys Acta. 1994 May 18;1185(3):327-35. doi: 10.1016/0005-2728(94)90248-8.
To evaluate the effects of phosphocreatine (PCr) and creatine (Cr) depletion on skeletal muscles of mice deficient in muscle creatine kinase (M-CK), we have fed mutant mice a diet containing the creatine analogue beta-guanidinopropionic acid (beta GPA). After 8-10 weeks of feeding, accumulation of the creatine analogue in M-CK-deficient muscles was comparable to that observed in muscles of wild-type mice. Strikingly, and unlike wild types, mutants did not accumulate phosphorylated beta GPA, indicating that MM-CK is the only muscle CK isoform which can phosphorylate beta GPA. In M-CK-deficient muscles there was respective depletion of PCr, Cr and ATP levels to 31, 41 and 83% of normal. The average cross-sectional area of type 2B fibres in gastrocnemius muscles was very much reduced and was similar to type 1 and type 2A fibres which maintained their normal size. The maximal isometric twitch force developed by gastrocnemius-plantaris-soleus (GPS) muscle complexes of beta GPA-treated mutants was reduced by about 30%, but these muscles showed an increased fatigue resistance during 1 and 5 Hz contraction. Mitochondrial enzyme activities in the upper hind limb musculature of null mutants were 20-35% increased by the beta GPA diet. Altogether, these results provide evidence that certain functions of the creatine kinase/phosphocreatine (CK/PCr) system are not eliminated solely by the loss of M-CK.
为了评估磷酸肌酸（PCr）和肌酸（Cr）耗竭对缺乏肌肉肌酸激酶（M-CK）的小鼠骨骼肌的影响，我们给突变小鼠喂食了含有肌酸类似物β-胍基丙酸（β-GPA）的饮食。喂食8-10周后，肌酸类似物在M-CK缺陷型肌肉中的积累与在野生型小鼠肌肉中观察到的相当。引人注目的是，与野生型不同，突变体没有积累磷酸化的β-GPA，这表明MM-CK是唯一能够磷酸化β-GPA的肌肉CK同工型。在M-CK缺陷型肌肉中，PCr、Cr和ATP水平分别降至正常水平的31%、41%和83%。腓肠肌中2B型纤维的平均横截面积大大减小，与保持正常大小的1型和2A型纤维相似。β-GPA处理的突变体的腓肠肌-比目鱼肌-跖肌（GPS）肌肉复合体产生的最大等长收缩力降低了约30%，但这些肌肉在1Hz和5Hz收缩期间表现出增强的抗疲劳能力。β-GPA饮食使无效突变体后肢上部肌肉组织中的线粒体酶活性提高了20%-35%。总之，这些结果提供了证据，证明肌酸激酶/磷酸肌酸（CK/PCr）系统的某些功能不会仅因M-CK的缺失而消除。
