Myosin ATPase dependence

Even though dynein, kinesin, and myosin serve similar ATPase-dependent chemomechanical functions and have structural similarities, they do not appear to be related to each other in molecular terms. Their similarity lies in the overall shape of the molecule, which is composed of a pair of globular heads that bind microtubules and a fan-shaped tail piece (not present in myosin) that is suspected to carry the attachment site for membranous vesicles and other cytoplasmic components transported by MT. The cytoplasmic and axonemal dyneins are similar in structure (Hirokawa et al., 1989 Holzbaur and Vallee, 1994). Current studies on mutant phenotypes are likely to lead to a better understanding of the cellular roles of molecular motor proteins and their mechanisms of action (Endow and Titus, 1992). 

Figure 9.21 The creatine/phosphocreatine shuttle in spermatozoa. This shuttle may not be present in all sperm it will depend upon the distance between the mitochondria and the flagellum. Mitochondria are present in the midpiece just below the head. ATP is required for movement of the flagellum which enables the sperm to swim. Dynein ATPase is the specific motor ATPase, similar to myosin ATPase, that transfers energy from ATP to the flagellum. A deficiency of creatine may explain low sperm motility in some infertile men. CK - creatine kinase. Deficiences of enzymes in the pathway for synthesis of creatine are known to occur (see Appendix 8.3).

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. 

Dynein, kinesin, and myosin are motor proteins with ATPase activity that convert the chemical bond energy released by ATP hydrolysis into mechanical work. Each motor molecule reacts cyclically with a polymerized cytoskeletal filament in this chemomechanical transduction process. The motor protein first binds to the filament and then undergoes a conformational change that produces an increment of movement, known as the power stroke. The motor protein then releases its hold on the filament before reattaching at a new site to begin another cycle. Events in the mechanical cycle are believed to depend on intermediate steps in the ATPase cycle. Cytoplasmic dynein and kinesin walk (albeit in opposite... 

Inhibitor of F-actin-myosin interaction (inhibitor of F-actin-dependent activation of ATPase) Troponin system (Tpl) Unphosphorylated myosin light chain... 

Tropomyosin and troponin are proteins located in the thin filaments, and together with Ca2+, they regulate the interaction of actin and myosin (Fig. 43-3) [5]. Tropomyosin is an a-helical protein consisting of two polypeptide chains its structure is similar to that of the rod portion of myosin. Troponin is a complex of three proteins. If the tropomyosin-troponin complex is present, actin cannot stimulate the ATPase activity of myosin unless the concentration of free Ca2+ increases substantially, while a system consisting solely of purified actin and myosin does not exhibit any Ca2+ dependence. Thus, the actin-myosin interaction is controlled by Ca2+ in the presence of the regulatory troponin-tropomyosin complex [6]. 

An enhancement of ATPase action comes through the phosphorylation of myosin light chains (MW 18,000). The phosphorylation is achieved because the high cellular [Ca2+] activates myosin kinase, an enzyme that contains calmodulin, a Ca2+-binding subunit. Phosphorylation of myosin is absolutely required for smooth muscle contraction, though not for the contraction of skeletal or cardiac muscle, because smooth muscle has no troponin. Thus, whereas contraction and relaxation in skeletal and cardiac muscle are achieved principally via the action of Ca2+ on troponin, in smooth muscle they must depend solely on the Ca2+-dependent phosphorylation of myosin. In skeletal and cardiac muscle, once the stimulus to the sarcolemma is removed, [Ca2+] in sarcoplasm drops rapidly back to 10 7 or 10 8 M via various Ca2+ pump mechanisms present in the sarcoplasmic reticulum, and tropomyosin can once again interfere with the myosin-actin interaction. 

NADH oxidation, and electron transport (Nriagu 1980). Cadmium is a potent enzyme inhibitor, affecting a variety of plant enzymes such as PEP carboxylase, lipase, invertase (Yu 1997), and others. Extensive reports are available concerning Cd-dependent inhibition of enzymes from animals and humans. Alkaline phosphatase and ATPases of myosin and pulmonary alveolar macrophage cells are examples. 

Caldesmon is a cytoplasmic protein with two isoform classes, one of which is found predominantly in smooth muscle cells and other cell types with partial myogenic differentiation. High-molecular-weight isoforms with molecular weights between 89 and 93 kD are capable of binding to actin, tropomyosin, calmodulin, myosin, and phospholipids, and they function to counteract actin-tropomyosin-activated myosin adenosine triphosphatase (ATPase). As such, they are mediators for the inhibition of calcium-dependent smooth muscle contraction." ... 

Figure 7.2. Some intracellular processes that may be affected by calcium channel blocking drugs. Calcium channel blocking drugs inhibit calmodulin-dependent sarcolemmal Ca2 -A TPase (7), myosin light-chain kinase (MLCK) (2) and phosphodiesterase (PDE) (7). Passive Na -Ca2 exchange (4) may also be inhibited, whilst (Na +K )-ATPase (J) is stimulated. Ca2 release from mitochondria (MIT) in exchange for Na ( ) may be inhibited, but the effect of calcium channel blocking drugs on Ca2 uptake into sarcoplasmic reticulum (SR) via Ca2 -ATPase (7) is variable.

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