ATPase activity

Many inhibitors of F F, are known [192-199] (Table 5.5), but the details of their mechanisms of inhibition during energization are unknown. In simplified F F,-liposomes, even Mg concentration had profound effects on P,-ATP exchange (7-fold) and inhibition by oligomycin and DCCD [197]. 

The proton translocating activity of Fq reconstituted into liposomes was measured [6,77] (Fig. 5.1). The channel activity of Fq is specific for H. The velocity of translocation = 31 jag ion per min per mg TFq, = 0.095 jag ion per liter) is somewhat proportional to AjaH+ (Ohm s law). This velocity is much slower than that of Na translocation through Na channels [77]. 

As described in Section 4.3, ATP-release from F,-ATP is the energy requiring step. The energy is indirectly supplied to F, from H -flux driven by via an 

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Succinimides. Ethosuximide [77-67-8] C2H22NO2 (41) and the related succinknide, methsuximide [77-41-8] C22H23NO2 (42) are used in absence seizure treatment. Like the other anticonvulsants discussed, the mechanism of action of the succinirnides is unclear. Effects on T-type calcium channels and -ATPase activity have been reported (20). Ethosuximide has significant CNS and gastrointestinal (GI) side effect HabiUties (13). 

Aminophenol is a selective nephrotoxic agent and intermpts proximal tubular function (121,122). Disagreement exists concerning the nephrotoxity of the other isomers although they are not as potent as 4-aminophenol (123,124). Respiration, oxidative phosphorylation, and ATPase activity are inhibited in rat kidney mitochondria (125). The aminophenols and their derivatives are inhibitors of 5-Hpoxygenase (126) and prostaglandin synthetase... 

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. 

Szent-Gyorgyi further showed that the viscosity of an actomyosin solution was lowered by the addition of ATP, indicating that ATP decreases myosin s affinity for actin. Kinetic studies demonstrated that myosin ATPase activity was increased substantially by actin. (For this reason, Szent-Gyorgyi gave the name actin to the thin filament protein.) The ATPase turnover number of pure myosin is 0.05/sec. In the presence of actin, however, the turnover number increases to about 10/sec, a number more like that of intact muscle fibers. 

However, release of ADP and P from myosin is much slower. Actin activates myosin ATPase activity by stimulating the release of P and then ADP. Product release is followed by the binding of a new ATP to the actomyosin complex, which causes actomyosin to dissociate into free actin and myosin. The cycle of ATP hydrolysis then repeats, as shown in Figure 17.23a. The crucial point of this model is that ATP hydrolysis and the association and dissociation of actin and myosin are coupled. It is this coupling that enables ATP hydrolysis to power muscle contraction. 

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... 

The myosins are a superfamily of proteins that have the ability to convert energy released by ATP is hydrolysis into mechanical work. There are many forms of myosin, all of which have ATPase activity and an actin-binding site that is located... 

Myosin-I molecules have several IQ sequences on or near the head and have light chains associated with them (Cheney and Mooseker, 1992 Cheney et al., 1993). Frequently, the light chains appear to be calmodulin molecules and some myosin-I molecules can bind three to four molecules of calmodulin at one time. Brush-border and adrenal myosin-I also bind calmodulin. Acanthamoeba myosin-I has a light chain that can be removed, in vitro, without adversely affecting the ATPase activity or the heavy chain phosphorylation (Korn and Hammer, 1988). The role of these calmodulin molecules in regulating myosin-I is complex and poorly understood. One possibility is that the calmodulin molecules dissociate from the heavy chains when calcium binds to the calmodulin, thereby imparting greater flexibility to the head of the myosin-I molecules. 

Myosin as an ATPase Activation of Myosin ATPase by Actin Lymn and Taylor Model 1971 Eisenberg and Hill Model 1985... 

The ATP in fatigued muscle is, however, well above the K , for actomyosin ATPase activity (Naiminga and Mommaerts, 1960). This indicates that the decrease in force generation is not related to a lack of ATP for crossbridge formation but... 

Van Der Laarse, W.J., LSnnergren, J., Diegenbach, P.C. (1991). Resistance to fatigue of single muscle fibers from Xenopus related to succinate dehydrogenase and myofibrillar ATPase activities. Exp. Physiol. 76, 589-596. 

In addition to marked perifascicular atrophy, infarctlike areas are sometimes seen, and are also consistent with a microangiopathy. Muscle fibers which appear normal morphologically may show loss of myofibrillar ATPase activity from the center of the fibers this is also characteristic of muscle subject to ischemia. Such changes may be reversible, but more prolonged ischemia undoubtedly causes irreversible muscle necrosis. 

Hwang J-S, Bogner E (2002) ATPase activity of the terminase subunit pUL56 of human cytomegalovirus. J Biol Chem 27 6943-6948... 

Struve, I., Weber, A., Liittge, U., Ball, E. Smith, J.A.C. (1985). Increased vacuolar ATPase activity correlated with CAM induction in Mesembryanthemum crystallinum and Kalanchoe blossfeldiana cv. Tom Thumb. Journal of Plant Physiology, 117, 451-68. 

Another important protein of the Clp family is ClpB which possesses ATPase activity. In a clpB mutation, 45% of the denatured and aggregated protein arising transiently after the transfer of an E. coli culture from 30 to 45 °C is stabilized [14]. ClpB seems to play an important role in the renaturation or proteolysis of the aggregated proteins, but the mechanism of action of ClpB is not yet known. One can suppose that it might participate in the resolubilization of aggregated proteins. 

Most chaperones show associated ATPase activity, with ATP or ADP being involved in the protein-chaperone interaction... 

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