Actomyosin ATPase reaction

In the so-called Lymm-Taylor model, the actomyosin ATPase reaction proceeds in a stepwise manner ... 

A combination of the novel flash photolysis technique enabling the rapid release of nucleotides such as ATP from inert, photolabile precursors (Kaplan et al., 1978 McCray et al., 1980 Gurney Lester, 1987) with the high x-ray intensities available from synchrotron sources has introduced the possibility of studying the kinetics of structural events associated with the actomyosin ATPase reactions in muscle fibres. The precursor or caged nucleotides can readily diffuse into skinned muscle fibres, where, in the case of caged-ATP, a pulse of ultraviolet (u.v.) light will photolyse... 

By using actomyosin ATPase reaction, analysis of untreated rat slow muscle soleus (SOL) revealed predominantly type 1 fibers with a few type 2A and 2B fibers. In contrast, the fast muscle EDL is composed predominantly of type 2 fibers with few type 1 fibers. Total fiber numbers are approximately 1,800 in SOL and 2,500 in EDL (Gupta et al, 1989). 

In the most recent work, Dawson et al (1978) have extended their muscle NMR studies to investigate the biochemical factors affecting muscular fatigue. The substances most directly involved in the transduction of chemical free energy into mechanical work in contracting muscle are ATP, ADP, Pi, H, and Mg all of these substances actually take part in the actomyosin-ATPase reactions which produce contraction. PCr is also involved in normal contractions of vertebrate muscles because the ATP that is hydrolyzed is rapidly rephosphorylated at the expense of PCr by the enzyme creatine phosphotransferase. Since P NMR can monitor all of these substances simultaneously, either directly or indirectly, it becomes possible to relate changes in them to concurrent changes in the mechanical performance of muscles. 

An insufficient rate of ATP resynthesis for optimal energy supply for actomyosin crossbridge formation and cycling, or for the additional ATPase reactions, Na" -K pumping and Ca reuptake and/or release by the SR. 

As an attempt to connect the first discussion, which was concerned with diffusion-reaction coupling, with Dr. Williams presentation of enzymes as dynamic systems, I wanted to direct attention to a number of specific systems. These are the energy-transducing proteins that couple scalar chemical reactions to vectorial flow processes. For example, I am thinking of active transport (Na-K ATPase), muscular contraction (actomyosin ATPase), and the light-driven proton pump of the well-known purple... 

It has generally been assumed that the energy required for muscular contraction was derived directly from the ATP split in the course of the reaction. The establishment of accurate relationships, however, has been hampered by the fact that the actomyosin ATPase continues to degrade the nucleotide long after contraction has reached an optimum. The availability of thrombosthenin with its much lower ATPase activity might be an interesting material for a comparative investigation of this basically important mechanism. 

The molecular events of contraction are powered by the ATPase activity of myosin. Much of our present understanding of this reaction and its dependence on actin can be traced to several key discoveries by Albert Szent-Gyorgyi at the University of Szeged in Hungary in the early 1940s. Szent-Gyorgyi showed that solution viscosity is dramatically increased when solutions of myosin and actin are mixed. Increased viscosity is a manifestation of the formation of an actomyosin complex. 

The Parallelism between ATPase Inhibition and the Inhibition of Various Actomyosin Reactions ... 

Solutions of F-actin and myosin at high ionic strength = 0.6) in vitro form a complex called actomyosin. The formation of the complex is reflected by an increase in viscosity and occurs in a deflnite molar ratio 1 molecule of myosin per 2 molecules of G-actin, the basic unit of the double-helical F-actin strand. It appears that a spike-like structure is formed, which consists of myosin molecules embedded in a backbone made of the F-actin double helix. Addition of ATP to actomyosin causes a sudden drop in viscosity due to dissociation of the complex. When this addition of ATP is followed by addition of Ca +, the myosin ATPase is activated, ATP is hydrolyzed and the actomyosin complex again restored after the ATP concentration decreases. Upon spinning of an actomyosin solution into water, flbers are obtained which, analogous to muscle flbers, contract in the presence of ATP. Glycerol extraction of muscle fibers removes all the soluble components and abolishes the semipermeability of the membrane. Such a model muscle system shows all the reactions of in vivo muscle contraction after the readdition of ATP and Ca +. This and similar model studies demonstrate that the muscle contraction mechanism is understood in principle, although some molecular details are still not clarified. 

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