Bittl J A, Ingwall J S
Circulation. 1987 Jan;75(1 Pt 2):I96-101.
The understanding of the physiologic role of the creatine kinase reaction has evolved in parallel with investigative technology. Since the creatine kinase reaction replenishes hydrolyzed ATP so rapidly, early studies detected only creatine phosphate hydrolysis during muscular contraction. Direct observation of ATP hydrolysis required creatine kinase inhibition and suggested that creatine phosphate provided an energy reserve. Elegant studies with isolated heart mitochondria provided evidence that the creatine kinase reaction regulates the rate of oxidative phosphorylation. The 31P nuclear magnetic resonance technique of magnetization transfer permitted the direct investigation of the creatine kinase reaction in intact organs and confirmed the classic observation that chemical flux through the creatine kinase reaction is coupled to mitochondrial energy production. Hearts from 18-month-old spontaneously hypertensive rats have as much as a 50% decrease in mitochondrial creatine kinase activity. Preliminary magnetization transfer studies in such a heart show a depressed relation between creatine kinase flux and cardiac performance. The results suggest that creatine kinase flux, as measured by magnetization transfer, is determined in part by creatine kinase isozyme composition and that these biochemical changes are associated with long-standing cardiac hypertrophy.
对肌酸激酶反应生理作用的理解是随着研究技术的发展而逐步深入的。由于肌酸激酶反应能如此迅速地补充水解的ATP，早期研究在肌肉收缩过程中仅检测到磷酸肌酸的水解。ATP水解的直接观察需要抑制肌酸激酶，这表明磷酸肌酸提供了一种能量储备。对分离的心脏线粒体进行的精细研究提供了证据，表明肌酸激酶反应调节氧化磷酸化的速率。磁化转移的31P核磁共振技术允许直接研究完整器官中的肌酸激酶反应，并证实了经典观察结果，即通过肌酸激酶反应的化学通量与线粒体能量产生相关联。18个月大的自发性高血压大鼠的心脏线粒体肌酸激酶活性降低多达50%。在这样的心脏中进行的初步磁化转移研究表明，肌酸激酶通量与心脏功能之间的关系减弱。结果表明，通过磁化转移测量的肌酸激酶通量部分由肌酸激酶同工酶组成决定，并且这些生化变化与长期存在的心脏肥大有关。
