Moerland T S, Kushmerick M J
Department of Biological Science, Florida State University, Tallahassee 32306.
Am J Physiol. 1994 Jul;267(1 Pt 1):C127-37. doi: 10.1152/ajpcell.1994.267.1.C127.
Mice were treated for 7-12 wk with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Treatment reduced total creatine to approximately 5% of control values in soleus (SOL) and extensor digitorum longus (EDL) muscles. In both muscles from treated mice, phosphorylated beta-GPA accumulated and resting [ATP] decreased by approximately 50%. Relative to controls, cytochrome oxidase and citrate synthase activities increased significantly in EDL from treated mice, but not in SOL; creatine kinase activity decreased significantly in SOL, but not in EDL. Measurements of poststimulation energy metabolism show that the energy cost to maintain tension in SOL and EDL from treated mice was approximately 50% of that in control muscle. Relative to controls, first-order rate constants of poststimulation O2 demand were 2- and 3.6-fold greater in SOL and EDL, respectively, from treated mice. Increased economy of SOL and EDL from treated mice is consistent with previously reported changes in myosin isoenzymes. Increases in rate constants of O2 utilization in creatine-depleted muscle are inconsistent with the hypothesis that cytoplasmic or mitochondrial creatine kinase is rate limiting for cellular respiration.
用肌酸类似物β-胍基丙酸（β-GPA）对小鼠进行7至12周的治疗。治疗后，比目鱼肌（SOL）和趾长伸肌（EDL）中的总肌酸降至对照值的约5%。在接受治疗的小鼠的这两块肌肉中，磷酸化β-GPA均有积累，且静息[ATP]下降了约50%。与对照组相比，接受治疗的小鼠的EDL中细胞色素氧化酶和柠檬酸合酶活性显著增加，但SOL中未增加；SOL中的肌酸激酶活性显著下降，但EDL中未下降。刺激后能量代谢的测量结果表明，维持接受治疗的小鼠的SOL和EDL中的张力所需的能量成本约为对照肌肉的50%。与对照组相比，接受治疗的小鼠的SOL和EDL中刺激后O2需求的一级速率常数分别高出2倍和3.6倍。接受治疗的小鼠的SOL和EDL经济性的提高与先前报道的肌球蛋白同工酶变化一致。肌酸耗尽的肌肉中O2利用速率常数的增加与细胞质或线粒体肌酸激酶是细胞呼吸速率限制因素这一假设不一致。
