Myosin hydrolyzing

In the relaxation phase of muscle contraction, the S-1 head of myosin hydrolyzes ATP to ADP and Pj, but these products remain bound. The resultant ADP-Pj-myosin complex has been energized and is in a so-called high-energy conformation. 

In resting muscle the high concentration of ADP does not decrease the proton gradient effectively and the high membrane potential slows electron transport. ADP, formed when ATP is hydrolyzed by myosin ATPase during contraction, may stimulate electron transport. However, the concentration of ATP (largely as its Mg salt) is buffered by its readily reversible formation from creatine phosphate catalyzed in the intermembrane space, and in other cell compartments, by the various isoenzymes of creatine kinase (reviewed by Walliman et al., 1992). 

Actin is a 42 kDa bent dumbbell-shaped globular monomer which is found in most eukaryotic cells. It is the primary protein of the thin (or actin) filaments. Also, by mass or molarity, actin is the largest constituent of the contractile apparatus, actually reaching millimolar concentrations. Actins from different sources seem to be more similar than myosins from the same sources. Actin binds ATP which is hydrolyzed to ADP, if the monomeric actin polymerizes. The backbone structure of the actin filament is a helix formed by two linear strands of polymerized actins like two strings of actin beads entwined. 

Because the equilibrium constant is close to one, this also means that the free energy does not change much when ATP is hydrolyzed. Most of the fall in free energy is associated with ATP binding to myosin as the equilibrium constant for this step is about 10 ° M. The binding energy is used to dissociate myosin from actin. 

The simplest mechanism to explain the much faster rate of dissociation of actomyosin-S-1 by ATP than that of ATP cleavage is that actin activates the myosin ATPase by accelerating the rate at which ADP and Pj are released. That is when ATP is added to actomyosin-S-1, ATP rapidly binds and dissociates actomyosin, myosin ATPase then hydrolyzes ATP to form myosin-ADP.Pj, this state then reattaches to actin and phosphate is released much faster from actomyosin. ADP.Pj than it is from myosin.ADP.Pj, as shown in the scheme below ... 

In summary, therefore, solution and fiber biochemistry have provided some idea about how ATP is used by actomyosin to generate force. Currently, it seems most likely that phosphate release, and also an isomerization between two AM.ADP.Pj states, are closely linked to force generation in muscle. ATP binds rapidly to actomyosin (A.M.) and is subsequently rapidly hydrolyzed by myosin/actomyosin. There is also a rapid equilibrium between M. ADP.Pj and A.M.ADP.Pj (this can also be seen in fibers from mechanical measurements at low ionic strength). The rate limiting step in the ATPase cycle is therefore likely to be release of Pj from A.M.ADP.Pj, in fibers as well as in solution, and this supports the idea that phosphate release is associated with force generation in muscle. 

When smooth muscle myosin is bound to F-actin in the absence of other muscle proteins such as tropomyosin, there is no detectable ATPase activity. This absence of activity is quite unlike the situation described for striated muscle myosin and F-actin, which has abundant ATPase activity. Smooth muscle myosin contains fight chains that prevent the binding of the myosin head to F-actin they must be phosphorylated before they allow F-actin to activate myosin ATPase. The ATPase activity then attained hydrolyzes ATP about tenfold more slowly than the corresponding activity in skeletal muscle. The phosphate on the myosin fight chains may form a chelate with the Ca bound to the tropomyosin-TpC-actin complex, leading to an increased rate of formation of cross-bridges between the myosin heads and actin. The phosphorylation of fight chains initiates the attachment-detachment contraction cycle of smooth muscle. 

The hydrolysis of ATP is used to drive movement of the filaments. ATP binds to myosin heads and is hydrolyzed to ADP and P, by the ATPase activity of the actomyosin complex. 

The myosin head hydrolyzes the bound ATP to ADP and Pj, but initially withholds the two reaction products. ATP cleavage leads to allosteric tension in the myosin head. 

Myosin-ATP complex is hydrolyzed rapidly to produce an conformationally energized state (often designated by an asterisk ). 

The interaction between actin and myosin, like that between all proteins and ligands, involves weak bonds. When ATP is not bound to myosin, a face on the myosin head group binds tightly to actin (Fig. 5-33). When ATP binds to myosin and is hydrolyzed to ADP and phosphate, a coordinated and cyclic series of conformational changes occurs in which myosin releases the F-actin subunit and binds another subunit farther along the thin filament. 

The cycle has four major steps (Fig. 5-33). In step (l), ATP binds to myosin and a cleft in the myosin molecule opens, disrupting the actin-myosin interaction so that the bound actin is released. ATP is then hydrolyzed in step (2), causing a conformational change in the protein to a high-energy state that moves the myosin head and changes its orientation in relation to the actin thin filament. Myosin then binds weakly to an F-actin subunit... 

As tightly bound ATP is hydrolyzed, a conformational change occurs. ADP and P remain associated with the myosin head. 

Myosins. There are 15 distinct families of proteins within the myosin superfamily.117 120 They vary greatly in size, but all of them bind and hydrolyze ATP, and all bind to actin. Most have C-terminal tails. At their N... 

In the second frame (b), strong bridges form between actin and myosin. This is followed by a structural alteration in the myosin molecules and an effective translocation of the thick filament relative to the thin filament in (c). During this process the ADP is released. After the translocation step, the bridge structure is broken by the binding of ATP, which is rapidly hydrolyzed to ADP and Pj. Each thick filament has about 500 myosin heads, and each head cycles about five times per second in the course of a rapid contraction. 

A) In resting muscle, ATP has been bound to myosin, then hydrolyzed to ADP and P,. 

Cell in resting state ATP hydrolyzed but products are still bound to myosin. 

E) Cell returns to resting state ATP hydrolyzed but products are still bound to myosin. The net effect of the five steps is the performance of work. Myosin ... 

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