Cross-bridge cycle

At this site, creatine kinase catalyses the phosphorylation of ADP by phosphocreatine with the production of ATP which, in turn, is used by the energy-requiring process that is, the cross-bridge cycle (Chapter 13). 

It simulates the activity of myosin ATPase, which results in contraction of the muscle (i.e. increased cross-bridge cycling). This increases the rate of utilisation of ATP and hence increases the concentration of ADP. 

The interaction between actin and myosin leads to contraction and the generation of force, in some cases very great force (Figure 13.9). The process is known as the cross-bridge cycle, the components of which are ... 

The sequence of events within muscle that leads to activation of the cross-bridge cycle, as described above, is... 

What factors limit the generation of ATP so that it does not meet the demand of the cross bridge cycle for ATP hydrolysis. An imbalance between demand and generation soon decreases the ATP/7YDP concentration ratio. 

The decrease in ATP/ADP concentration ratio, since it decreases the energy released on hydrolysis of ATP which could decrease two processes that would result directly in fatigue the cross bridge cycle and the Na+/K+ ion ATPase (Figure 13.24). 

An increase in the proton concentration since it inhibits three processes that are part of the sequence by which Ca + ion release from the SR activates the cross bridge cycle (Figure 13.25). 

Figure 13.25 Processes in the muscle fibre that are inhibited by protons (H ) that could directly or indirectly reduce the rate of cross-bridge cycling. The increase in proton concentration inhibits (i) Ca ion release from the reticulum (ii) Ca ion binding to troponin-C (hi) Ca ion activation of the cross bridge cycle (Donaldson et al. 1978).

Figure 22.12 Regulation of actin-myosin interaction in smooth muscle via the light-chain kinase and phosphatase and effect on blood pressure. ions bind to calmodulin and the complex stimulates the conversion of inactive myosin light chain kinase (MLCK) to active MLCK which then phosphorylates the light chain. This results in activation of the cross-bridge cycle. The overall effect is vasoconstriction of the arteriole, which increases blood pressure.

Myosin, which increases the rate of the cross-bridge cycling. 

The cause of the decreased contractile activity is likely to be due to a decrease in ATP/ADP concentration ratio in the cardiomyocyte, since hydrolysis of ATP now results in less energy being transfered for each molecule of ATP that is hydrolysed. That is, sufficient energy is not available to power the maximum rate of the cross-bridge cycle or power the transport of ions across the plasma membrane (e.g. the Na+/K+ pump or the ion channels). Changes in concentrations of such ions can lead to disturbance of electrical activity that controls the contractions of the fibres. 

Over the last twenty years biophysical work on this preparation has concentrated mainly on the elucidation of the filament structure and cross-bridge conformations (Reedy et al., 1965 Squire et al., 1977 Wray, 1979 Clarke et al., 1986 Reedy et al., 1987), and on the mechanical characterisation of various equilibrium states and of the kinetics of the cross-bridge cycle (Jewell Ruegg, 1%6 White, 1970 Tregear, 1977 Gtith et al., 1981 White Thorson, 1983). The biochemistry of ATP hydrolysis by the insect proteins has received less attention than that of vertebrate muscle proteins, primarily because of shortage of tissue, but recently aspects of the biochemical kinetics have been investigated (White et al., 1986). 

Mackey, A. T., and Gilbert, S. P. (2003). The ATPase cross-bridge cycle of the Kar3 motor domain implications for single head motility./. Biol. Chem. 278, 3527-3535. 

Dillon, P.F., Aksoy, M.O., Driska, S.P. and Murphy, RA. (1981). Myosin phosphorylation and the cross-bridge cycle in smooth muscle. Science (Wash). DC211, 495-497. 

Thus, in the cross-bridge cycle, myosin is bound with high affinity alternately to actin and to ATP. Since the energy changes associated with myosin binding to actin and MgATP are internal to the system, the only free energy... 

It is important to note that this model predicts the hydrolysis of one ATP for every cross-bridge cycle of every myosin head there is evidence that, in high-speed contractions at least, there may be multiple attachments and detachments per hydrolysis. Thus, our understanding is obviously not complete. Nevertheless, the ATP consumption associated with contraction can be enormous. The metabolic scope (ratio of maximal to resting energy consumption) of skeletal muscle can reach 100 1, and there must necessarily be metabolic specializations to meet this peak demand and to do so quickly. Energy metabolism is discussed in Chapters 13-15 and 18. 

To understand how a muscle contracts, consider the Interactions between one myosin head (among the hundreds In a thick filament) and a thin (actin) filament as diagrammed In Figure 3-25. During these cyclical Interactions, also called the cross-bridge cycle, the hydrolysis of ATP Is coupled to the movement of a myosin head toward the Z disk, which corresponds to the (+) end of the thin filament. Because the thick filament Is bipolar, the action of the myosin heads at opposite ends of the thick filament draws the thin filaments toward the center of the thick filament and therefore toward the center of the sarcomere (Figure 19-23). This movement shortens the sarcomere until the ends of the thick filaments abut the Z disk or the (—) ends of the thin filaments overlap at the center of the A band. Contraction of an Intact muscle results from the activity of hundreds of myosin heads on a single thick filament, amplified by the hundreds of thick and thin filaments In a sarcomere and thousands of sarcomeres In a muscle fiber. 

Table I illustrates the variability of the amino-terminal residues of several different actin isoforms. Mutagenesis in this region can result in partial or complete inhibition of F-actin motility (Sutoh, 1993), consistent with the site being a likely initial target for myosin during the cross-bridge cycle (Rayment et al., 1993b). In fact, numerous studies also have identified several domains of the actin molecule representing clusters of amino acids specifically involved in monomer-monomer interactions (Holmes et al., 1990 Hennessey et al., 1993 Khaitlina et al., 1993 Labbe et al., 1994), actin-myosin interactions (Holmes and Kabsch, 1991 Hennessey et al., 1993 Schroder et al.,...

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