Muscle specificity

Creatine phosphate is formed from ATP and creatine (Figure 49-16) at times when the muscle is relaxed and demands for ATP are not so great. The enzyme catalyzing the phosphorylation of creatine is creatine kinase (CK), a muscle-specific enzyme with clinical utility in the detection of acute or chronic diseases of muscle. 

Shanske, S Sakoda, S Hermodson, M. A., DiMauro, S and Schon, E. A., Isolation of a cDNA encoding the muscle-specific subunit of human phosphoglycerate mutase. J. Biol. Chem. 262, 14612-14617(1987). 

FIGURE 11-7 Gene structure of AChE. Alternative cap sites in the 5 end of the gene allow for alternative promoter usage in different tissues. Skeletal-muscle-specific regulation is controlled by the intron region between Exons 1 and 2. Exons 2, 3 and 4 encode an invariant core of the molecule that contains the essential catalytic residues. Just prior to the stop codon, three splicing alternatives are evident 1, a continuation of exon 4 2, the 4-5 splice and 3, the 4-6 splice. The catalytic subunits produced differ only in their carboxy-termini and are shown in the lower panel. (Modified with permission from reference [24].)... 

Deficiency of the muscle-specific myoadenylate deaminase (MADA) is a frequent cause of exercise-related myopathy and is thought to be the most common cause of metabolic myopathy. MADA catalyzes the deamination of AMP to IMP in skeletal muscle and is critical in the purine nucleotide cycle. It is estimated that about 1-2% of all muscle biopsies submitted to medical centers for pathologic examination are deficient in AMP deaminase enzyme activity. MADA is 10 times higher in skeletal muscle than in any other tissue. Increase in plasma ammonia (relative to lactate) after ischemic exercise of the forearm may be low in this disorder, which is a useful clinical diagnostic test in patients with exercise-induced myalgia... 

The putative receptor for agrin is a RPTK known as muscle-specific kinase (MuSK). The extracellular domain of MuSK resembles that of the ROR family of RPTKs, while the kinase domain is similar to that of the Trk neurotrophic receptor (Fig. 24-6). MuSK is expressed at low concentrations in proliferating myoblasts and is induced... 

Antibodies against the muscle-specific receptor kinase mimic myasthenia gravis 724... 

LDL low density lipoprotein MuSK muscle-specific kinase... 

Huang J, Kato K, Shibata E, et al. 1989. Effects of chronic w-hexane exposure on nervous system-specific and muscle-specific proteins. Arch Toxicol 63(5) 381-385. 

Carnitine Acyltransferase (CAT/CPT) Deficiency (Myopathic Form). Although all tissues with mitochondria contain carnitine acyltransferase, the most common form of this genetic deficiency is myopathic and due to a defect in the muscle-specific CAT/CPT gene. Hallmarks of this disease include ... 

Fig. 29. Thirteen-year-old boy with Duchenne Dystrophy, (a) The fat selective image shows a fatty degeneration of all muscles in a cross-section of the lower limb. The fat tissue is orientated in the direction of the muscle fibres, and is present between the fibres and in the septa, (b, c) The spectra from both volume elements indicated in (a) reveal signals from EMCL. Muscle specific metabolites (TMA and creatine) are clearly reduced and not visible in the proton spectra due to the reduction of muscle tissue in favour of adipose tissue.

In a study with 3 EMS patients the relative signal intensities in proton spectra recorded at an echo time of 50 ms with a repetition time of 2 s were quantitatively compared with healthy controls. It was evident that the muscle specific signals from TMA and Cr are relatively low in EMS patients (TMA 0.20-0.43% in the patients and 0.47-0.68% in the controls creatine 0.32-0.60% in the patients and 0.48-0.77% in the controls) probably indicating changes of concentrations and altered chemical surroundings of TMA and Cr in the myoplasm of the diseased cells. The overall lipid signal was found to be... 

Muscle-specific auxiliary reactions for ATP synthesis exist in order to provide additional ATP in case of emergency. Creatine phosphate (see B) acts as a buffer for the ATP level. Another ATP-supplying reaction is catalyzed by adenylate kinase [1] (see also p.72). This disproportionates two molecules of ADP into ATP and AMP. The AMP is deaminated into IMP in a subsequent reaction [2] in order to shift the balance of the reversible reaction [1 ] in the direction of ATP formation. 

Pyruvate kinase-muscle isozyme Muscle-specific phosphorylase kinase Lysosomal acid a-glucosidase... 

Nunnally, M.H. Rybicki, S.B. Stull, J.T. Characterization of chicken skeletal muscle myosin light chain kinase. Evidence for muscle-specific isozymes. J. Biol. Chem., 260, 1020-1026 (1985)... 

Harder, G. McGowan, R. Isolation and characterization of the muscle-specific isoform of creatine kinase from the zebrafish, Danio rerio. Biochem.-Cell Biol., 79, 779-782 (2001)... 

Muscle, whose structure and function are discussed in Chapter 19, develops in response to four members of the myoD family. These include myoD, myogenin, myf5, and MRF4.417-419 All are muscle-specific transcription factors of the basic helix -loop -helix class. An unusual aspect of muscle development is formation of multinucleate myotubes (muscle fibers p. 1096)420 Apoptosis plays an important role in muscle development and can present significant complications in damaged cardiac muscle.421 Defects in several developmental control genes are responsible for congenital heart diseases.422... 

Figure 12.8 Model for general and cell-specific plasmid nuclear import. (A) SV40 enhancer-mediated nuclear import. Because the transcription factors bound by this DNA sequence are ubiquitously expressed, SV40 DNA localizes to the nuclei of all cell types (see Table 12.1). (B) Smooth muscle-specific plasmid nuclear import. Smooth muscle-specific transcription factors, including SRF among others, can bind to their target sites within the SMGA promoter carried on a plasmid and serve to transport the DNA to the nucleus via interactions with the NLS-mediated protein import machinery. Since these factors are not expressed in other cell types, no nuclear import will occur in non-smooth muscle cells.

Browning, C.L., Culberson, D.E., Aragon, I.V., Fillmore, R.A., Croissant, J.D., Schwartz, R.J. et al. (1998) The developmental regulated expression of serum response factor plays a key role in the control of smooth muscle-specific genes. Dev. Biol., 194, 18-37. 

Li, S., MacLaughlin, F.C., Fewell, J.G., Gondo, M., Wang, J., Nicol, F. et al. (2001) Muscle-specific enhancement of gene expression by incorporation of the SV40 enhancer in the expression plasmid. Gene Ther., 8, 494 197. 

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