Shoubridge E A, Challiss R A, Hayes D J, Radda G K
Biochem J. 1985 Nov 15;232(1):125-31. doi: 10.1042/bj2320125.
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.
给大鼠喂食含1%β-胍基丙酸（GPA，一种肌酸底物类似物）的饮食6至10周，以耗尽其肌肉中的肌酸。先前的研究表明，这种处理可使骨骼肌和心肌中的[磷酸肌酸]降低90%，仅使骨骼肌中的[ATP]降低50%。在腓肠肌的浅白色、内侧和深红色部分、比目鱼肌和跖肌以及心脏中，测量了肌酸激酶以及有氧和无氧能量代谢代表性酶的最大活性。喂食GPA的动物的快肌比对照组小，但比目鱼肌的大小没有变化。除腓肠肌浅层外，所有快肌区域的有氧酶活性增加了30 - 40%，但比目鱼肌中的活性没有变化。除腓肠肌深层外，所有骨骼肌区域的肌酸激酶和磷酸果糖激酶活性降低了20 - 50%，糖原磷酸化酶的活性通常与这些变化平行。所测心脏中任何酶的活性均无显著变化。喂食GPA的大鼠中，腓肠肌 - 跖肌复合体的糖原含量增加了185%。比目鱼肌中I型纤维的比例从对照大鼠的81%增加到喂食GPA大鼠的100%，这与先前关于该肌肉等长收缩特性改变和最大缩短速度降低的报道一致[彼得罗夫斯基和菲奇（1980年）《普弗吕格尔斯文献》384卷，123 - 129页]。我们得出结论，快肌通过缩短扩散距离、增加有氧能力和降低糖酵解潜能来适应。慢肌降低糖酵解潜能并变得更慢，从而降低能量需求。这些结果表明，[磷酸肌酸]和[ATP]的持续变化足以改变酶蛋白和收缩装置蛋白的表达，并且转化反应存在纤维类型特异性阈值。
