Skeletal muscle metabolism nucleotides

Coordinated regulation of skeletal muscle metabolism by nucleotides. 

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... 

K3. Kendrick-Jones, J., and Perry, S. V., The enzymes of adenine nucleotide metabolism in developing skeletal muscle. Biochem. J. 103, 207-214 (1967). 

The operation of the cycle produces large quantities of the reduced forms of the nucleotides of adenine with nicotinamide (NAD and NADP) and ribo-flavine (FP). The regeneration of these coenzymes is effected by a transfer of electrons from the reduced forms to the oxygen of the atmosphere. In almost every kind of living cell, this transfer is mediated by some or all of the cytochrome respiratory chain (Section 5.4.3). Most of the organisms that lack all cytochromes have insignificant aerobic metabolism. Few enzymatic differences in the cycle have been demonstrated in mammals, but in the rat there is six times more aconitate hydratase in the heart than in skeletal muscle (Dixon and Webb, 1979). 

Calmodulin, an intracellular calcium-combining protein, is involved in many bodily processes such as secretion, activation of myosin kinase, and cyclic nucleotide metabolism. A similar protein, troponin-r, regulates conformational changes in skeletal muscle. The control of skeletal muscle contraction depends entirely on intracellular calcium. Hence those drugs such as nifedepine (Section 14.2) which block calcium channels, have no effect. On the other hand, smooth and cardiac muscles are much influenced by external calcium levels. 

The results of all these experiments with rabbits may be explained as being due to an increased synthesis of DNA in skeletal muscle of the vitamin E-deficient animals with no appreciable change in the nucleic acid metabolism of other tissues. This increased rate of DNA synthesis in skeletal muscle from vitamin E-deficient animals would require an accelerated rate of synthesis of acid-soluble nucleotides, which in turn could result in higher specific activities of nucleic acids isolated from other tissues... 

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