ATPases skeletal muscle

The trigger for all musele eontraetion is an increase in Ca eoneentration in the vicinity of the muscle fibers of skeletal muscle or the myocytes of cardiac and smooth muscle. In all these cases, this increase in Ca is due to the flow of Ca through calcium channels (Figure 17.24). A muscle contraction ends when the Ca concentration is reduced by specific calcium pumps (such as the SR Ca -ATPase, Chapter 10). The sarcoplasmic reticulum, t-tubule, and sarcolemmal membranes all contain Ca channels. As we shall see, the Ca channels of the SR function together with the t-tubules in a remarkable coupled process. 

Sandwich complexes nickel. 5, 35 Sapphyrins, 2, 888 demetallation, 2, 891 metallation, 2, 891 reactions, 2, 891 synthesis, 2, 889 Sarcoplasmic reticulum calcium/magnesium ATPase, 6, 566 skeletal muscle... 

Figure 14. Normal skeletal muscle showing random distribution of type 1 (dark), type 2A (pale) and type 2B (intermediate) fibers myofibrillar ATPase after pH 4.6 preincubation.

The P-alanyl dipeptides carnosine and anserine (A -methylcarnosine) (Figure 31-2) activate myosin ATPase, chelate copper, and enhance copper uptake. P-Alanyl-imidazole buffers the pH of anaerobically contracting skeletal muscle. Biosynthesis of carnosine is catalyzed by carnosine synthetase in a two-stage reaction that involves initial formation of an enzyme-bound acyl-adenylate of P-alanine and subsequent transfer of the P-alanyl moiety to L-histidine. 

Figure 49-8. Diagram of the relationships among the sarcolemma (plasma membrane), a T tubule, and two cisternae of the sarcoplasmic reticulum of skeletal muscle (not to scale). The T tubule extends inward from the sarcolemma. A wave of depolarization, initiated by a nerve impulse, is transmitted from the sarcolemma down the T tubule. It is then conveyed to the Ca release channel (ryanodine receptor), perhaps by interaction between it and the dihydropyridine receptor (slow Ca voltage channel), which are shown in close proximity. Release of Ca from the Ca release channel into the cytosol initiates contraction. Subsequently, Ca is pumped back into the cisternae of the sarcoplasmic reticulum by the Ca ATPase (Ca pump) and stored there, in part bound to calsequestrin.

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. 

SERCA la denotes the Ca -ATPase of adult fast-twitch skeletal muscle with glycine at its C-terminus in the rabbit [53,58], and alanine at the C-terminus in the chicken [59,60]. The C-terminus of the lobster enzyme is apparently blocked [59]. 

SERCA2a is the principal form of the Ca -ATPase in adult slow-twitch skeletal and cardiac muscles and in neonatal skeletal muscles [8,9,42,53,54,67]. It is also... 

The first Ca -ATPase clones were isolated by probing cDNA libraries with radiolabeled synthetic oligonucleotides [42] that represented an established amino acid sequence ((Trp-) Phe Met Tyr Ala) in the fast-twitch skeletal muscle... 

Fig. 1. Amino acid sequence homology between the neonatal fast-twitch and slow-twitch skeletal muscle forms of the Ca -ATPase. The sequence of the slow Ca -ATPase is shown above the neonatal fast-twitch form, with nonhomologous amino acids indicated by asterisks. The sequence of the slow ATPase is shifted to the right by one residue at residue 505 to allow realignment after the difference in sequence length. Ml-MlO, membrane spanning regions S1-S5, stalk sectors Tl, T2, major tryptic cleavage sites P,...

The cDNA clone for the neonatal rabbit fast-twitch skeletal muscle Ca -ATPase encodes for 1001 amino acids giving a product with an estimated molecular weight of 110 331 Da [8], The clone for the Ca -ATPase of slow-twitch skeletal muscle sarcoplasmic reticulum (S-Ca -ATPase) encoded for 997 amino acids with a relative molecular mass (Mr) of 109 529 kDa [42],... 

Sarcoplasmic reticulum vesicles prepared from rabbit skeletal muscle were crystallized in a medium of 0.1 M KCl, lOmM imidazole (pH 8), and 5mM MgCl2 by the addition of either CaCl2 (100/rM) or lanthanide ions (1-8 M) that stabilize the E conformation of the Ca -ATPase [119]. After incubation at 2°C for 5-48 hours, crystalline arrays were observed on the surface of about 10 20% of the vesicles in sarcoplasmic reticulum preparations obtained from fast-twitch rabbit skeletal muscles. 

A wide selection of monoclonal and polyclonal anti-Ca -ATPase antibodies have become available in recent years. Studies with these antibodies defined the localization of Ca " -ATPase in the sarcoplasmic reticulum of developing and mature skeletal muscles [60,262-270] and established a pattern of cross reactivity with various Ca -ATPase isoenzymes in the sarco(endo)plasmic reticulum [270-286] and in the plasma membrane [284,287-290] of skeletal, cardiac and smooth muscles. Antibodies have also proved useful in the quantitation of Ca -ATPase, both in muscles of diverse fiber types [291-294] and in COS-1 cells transfected with Ca -ATPase cDNA [97,103,126,127,129,215],... 

In smooth muscle, myosin crossbridges have less myosin ATPase activity than those of skeletal muscle. As a result, the splitting of ATP that provides energy to "prime" the crossbridges, preparing them to interact with actin, is markedly reduced. Consequently, the rates of crossbridge cycling and tension development are slower. Furthermore, a slower rate of calcium removal causes the muscle to relax more slowly. 

Mahaney, J. E., Thomas, D. D. and Froehlich, J. P. The time-dependent distribution of phosphorylated intermediates in native sarcoplasmic reticulum Ca2+-ATPase from skeletal muscle is not compatible with a linear kinetic model. Biochemistry 43 4400-4416, 2004. 

Odermatt, A., Taschner, P. E., Khanna, V. K. etal. Mutations in the gene-encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, are associated with Brody disease. Nat. Genet.lA. 191-194,1996. 

Odermatt A, Barton K, Khanna VK et al 2000 The mutation of Pro789 to Leu reduces the activity of the fast-twitch skeletal muscle sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) and is associated with Brody disease. Hum Genet 106 482-491... 

As further tissues were examined it became evident that the details of mitochondrial morphology were very variable. While most cells had rod-or sausage-shaped organelles, some were spherical. Other cells had mitochondria with spiral cristae or with massive crystalline inclusions. In confirmation of earlier suggestions from classical microscopists the position of mitochondria in cells was also seen to be linked with the site in the cell where energy was required. In skeletal muscle the mitochondria were adjacent to the myofibrils in the renal tubules they were close to the inner (non-luminal) surface of the cell which was then found to be the location of the Na/K-ATPase involved in active... 

Smooth muscle differs from skeletal muscle in various ways. Smooth muscles—which are found, for example, in blood vessel walls and in the walls of the intestines—do not contain any muscle fibers. In smooth-muscle cells, which are usually spindle-shaped, the contractile proteins are arranged in a less regular pattern than in striated muscle. Contraction in this type of muscle is usually not stimulated by nerve impulses, but occurs in a largely spontaneous way. Ca (in the form of Ca -calmodulin see p.386) also activates contraction in smooth muscle in this case, however, it does not affect troponin, but activates a protein kinase that phosphorylates the light chains in myosin and thereby increases myosin s ATPase activity. Hormones such as epinephrine and angiotensin II (see p. 330) are able to influence vascular tonicity in this way, for example. 

The catecholamines can play an important role in the short-term regulation of plasma potassium levels. Stimulation of hepatic a-adrenoceptors will result in the release of potassium from the liver. In contrast, stimulation of (32-adrenoceptors, particularly in skeletal muscle, will lead to the uptake of potassium into this tissue. The (32-adrenoceptors are linked to the enzyme Na"", K+ adenosine triphosphatase (ATPase). Excessive stimulation of these (32-adrenoceptors may produce hypokalemia, which in turn can be a cause of cardiac arrhythmias. 

The best studied example of a Group IIA cation transport system is the calcium pump of the sarcoplasmic reticulum of skeletal muscle. Indeed, the calcium pump and the sodium pump represent the most studied of all transport processes. The calcium pump involves a membrane-bound (Ca2+, Mg2+)-ATPase and uptake of Ca2+ is associated with hydrolysis of ATP. While the... 

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