Kinetics and energetics of the crossbridge cycle.
Kinetics and energetics of the crossbridge cycle.
复制标题
跨桥循环的动力学和能量学。
DOI：
10.1007/s10741-005-5248-2
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发表时间：
2005
影响因子：
4.6
通讯作者：
Maughan,DavidW
中科院分区：
文献类型：
--
作者：
Maughan,DavidW
肌凝蛋白头部与肌动蛋白丝相互作用，这一过程由MgATP推动，由钙调节，为人类心脏的泵状运动提供动力。MgATP的水解，MgATP及其水解产物与肌动蛋白结合的竞争，以及竞争中亲和关系的转移顺序，构成了肌肉收缩的主要机制。在心脏周期中产生的力、功和能量源于肌凝蛋白头部的异构化，这与肌动蛋白与肌凝蛋白的强结合和磷酸盐的释放密切相关。当细胞内[Ca2+]与肌钙蛋白结合的波动和细丝上原肌球蛋白的相关移动在搏动基础上调节交叉桥的数量时，产生的振荡工作被舒张期间发展的拉伸延迟力响应所增强。这种拉伸激活的肌生成反应是由特殊的肌丝结构促进的，包括肌凝蛋白基本轻链的肌动蛋白结合部分和肌凝蛋白结合蛋白C，它们被认为指导和定向肌凝蛋白头部或增强细丝激活。肌凝蛋白调节轻链、肌凝蛋白结合蛋白C和肌钙蛋白T的磷酸化也有助于这方面。动物模型显示肌球蛋白和其他肌原纤维蛋白的异构体变化对能量输出有重要影响，但人类心肌的异构体变化充其量是适度的，因此与收缩蛋白的疾病相关翻译后修饰及其化学环境的变化相比，可能在调节过桥动力学中只起次要作用。
Myosin heads interacting with actin filaments, a process fueled by MgATP and regulated by calcium, powers the pump-like action of the human heart. Hydrolysis of MgATP, the competition between MgATP, its products of hydrolysis, and actin for binding to myosin, and the sequence of shifting affinities in that competition, constitute the central mechanism of muscular contraction. The force, work, and power produced during the cardiac cycle stems from an isomerization of the myosin head that is closely associated with strong binding of myosin to actin and release of phosphate. While fluctuations of intracellular [Ca2+] bound to troponin and related shifts in tropomyosin on the thin filaments regulate the number of crossbridges on a beat-to-beat basis, the oscillatory work produced is augmented by a delayed force response to stretch that develops during diastole. This stretch-activated myogenic response is facilitated by specialized myofilament structures, including actin-binding portions of the myosin essential light chain and myosin binding protein C, which are thought to guide and orient the myosin head or enhance thin filament activation. Phosphorylation of the myosin regulatory light chain, myosin binding protein C, and troponin T also assist in this regard. Animal models show isoform shifts in myosin and other myofibrillar proteins have major effects on power output, but isoform shifts in human myocardium are modest at best and are therefore likely to play only a minor role in modulating crossbridge kinetics compared to disease-related post-translational modifications of the contractile proteins and to changes in their chemical environment.