Biochemical adaptation in the skeletal muscle of rats depleted of creatine with the substrate analogue beta-guanidinopropionic acid.
Biochemical adaptation in the skeletal muscle of rats depleted of creatine with the substrate analogue beta-guanidinopropionic acid.
复制标题
用底物类似物β-胍基丙酸耗尽肌酸的大鼠骨骼肌的生化适应。
作者：
E. Shoubridge;R. Challiss;D. J. Hayes;G. Radda
大鼠被喂食含有1% β -胍丙酸（GPA）的饮食（一种肌酸底物类似物）6-10周，以消耗肌肉中的肌酸。先前的研究表明，这种操作可以使骨骼肌和心肌中的[磷酸肌酸]减少90%，仅骨骼肌中的[ATP]减少50%。在腓肠肌白色浅部、中间部分和深红色部分、比目鱼肌和跖肌以及心脏部位测定了肌酸激酶和有氧和无氧能量代谢代表性酶的最大活性。gpa喂养的动物的快速收缩肌肉比对照组小，但比目鱼肌的大小没有变化。除腓肠肌浅表外，所有快肌区有氧酶活性均增加30-40%，但比目鱼肌活性不变。肌酸激酶和磷酸果糖激酶的活性在除腓肠肌深层外的所有骨骼肌区域均下降了20-50%，糖原磷酸化酶的活性基本与这些变化相一致。在心脏中测量到的任何一种酶的活性都没有明显的变化。大鼠灌喂gpa后，腓肠肌-植物复合体的糖原含量增加了185%。I型纤维在比目鱼肌中的比例从对照大鼠的81%增加到gpa喂养大鼠的100%，这与先前关于改变等距抽搐特征和该肌肉最大缩短速度降低的报道一致[Petrofsky & Fitch (1980) Pflugers Arch. 384, 123-129]。我们得出结论，快速收缩肌肉通过减少扩散距离，增加有氧能力和降低糖酵解电位的组合来适应。慢收缩肌肉会降低糖酵解电位，变得更慢，从而减少能量需求。这些结果表明，仅[磷酸肌酸]和[ATP]的持续变化就足以改变酶蛋白和收缩器官蛋白的表达，并且存在纤维类型特异性阈值以进行转化反应。
Rats were fed on a diet containing 1% beta-guanidinopropionic acid (GPA), a creatine substrate analogue, for 6-10 weeks to deplete their muscle of creatine. This manipulation was previously shown to give a 90% decrease in [phosphocreatine] in skeletal and cardiac muscle and a 50% decrease in [ATP] in skeletal muscle only. Maximal activities of creatine kinase and of representative enzymes of aerobic and anaerobic energy metabolism were measured in the superficial white, medial and deep red portions of the gastrocnemius muscle, in the soleus and plantaris muscle and in the heart. Fast-twitch muscles were smaller in GPA-fed animals than in controls, but the size of the soleus muscle was unchanged. The activities of aerobic enzymes increased by 30-40% in all fast-twitch muscle regions except the superficial gastrocnemius, but were unchanged in the soleus muscle. The activities of creatine kinase and phosphofructokinase decreased by 20-50% in all skeletal-muscle regions except the deep gastrocnemius, and the activity of glycogen phosphorylase generally paralleled these changes. There were no significant changes in the activities of any of the enzymes measured in the heart. The glycogen content of the gastrocnemius-plantaris complex was increased by 185% in GPA-fed rats. The proportion of Type I fibres in the soleus muscle increased from 81% in control rats to 100% in GPA-fed rats, consistent with a previous report of altered isometric twitch characteristics and a decrease in the maximum velocity of shortening in this muscle [Petrofsky & Fitch (1980) Pflugers Arch. 384, 123-129]. We conclude that fast-twitch muscles adapt by a combination of decreasing diffusion distances, increasing aerobic capacity and decreasing glycolytic potential. Slow-twitch muscles decrease glycolytic potential and become slower, thus decreasing energy demand. These results suggest that persistent changes in the [phosphocreatine] and [ATP] are alone sufficient to alter the expression of enzyme proteins and proteins of the contractile apparatus, and that fibre-type-specific thresholds exist for the transformation response.