Muscle nucleotide metabolism

Bilyk, T.I. (1989). Impact of environmental factors on the adenyl nucleotide metabolism in fish muscle and liver (In Russian). Gidrobiologicheskii Zhurnal 25, 58-65. 

Muscle can metabolize AMP by using the purine nucleotide cycle. The initial step in this cycle, catalyzed by AMP deaminase, is the conversion of AMP into IMP. 

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

Role of purine nucleotides in muscle energy metabolism. The conversion of AMP to IMP prevents loss of adenosine from the cell. 

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 enzymes of the pentose phosphate pathway are widely distributed in plants, animals, and microorganisms. Recently attempts have been made to evaluate the activity of this system in vivo. Isotope experiments, in which the rate of conversion of C-1 of glucose to CO2 is compared with the rate of CO2 formation from other atoms of glucose, indicate that a major part of the oxidation in liver may proceed by the pentose pathway. In contrast, glycolysis accounts for essentially all of muscle carbohydrate metabolism. The presence of Zwischenferment, however, does not imply that this cyclic mechanism is operative, since the first steps may be used for the production of pentose phosphate for nucleotide synthesis, polysaccharides, or other purposes. 

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... 

Phosphorus is found in every cell of the body, but most of it (about 80% of the total) is combined with calcium as Ca3(P04)2 in the bones and teeth (Harper 1969 Tietz 1970). Phosphorus is present in cells mainly as organic phosphate, with a small amount in serum as inorganic phosphate (Tietz 1970). Phosphorus is involved in the intermediary metabolism of carbohydrates (Tietz 1970). About 10% is found in combination with proteins, phospholipids, and carbohydrates and in other compounds in the blood and muscle (Harper 1969). The remaining phosphorus is widely distributed in various chemical compounds such as nucleic acids, nucleotides, and adenosine triphosphate (ATP) (Tietz 1970). 

Muscle tissue contains two glycerol-3-phosphate dehydrogenases a cytosolic enzyme, which uses NADH, and a flavin-nucleotide-dependent mitochondrial enzyme. What is the metabolic significance of these two enzymes ... 

Japanese workers (KIO) have reported the occasional appearance of NAD in the urine of patients with progressive muscular dystrophy. Coenzyme A is said to be decreased in the muscle and increased in the serum of patients (Rl). Such changes probably reflect increased leakage of these nucleotides from diseased muscle fibers rather than changes in their metabolism. 

Coordinated regulation of skeletal muscle metabolism by nucleotides. 

Most of the oxygen consumed by an animal is used by its muscle, and in the presence of a fall in local temperature, oxygen supply to ischemic muscle is adequate for normal metabolic demands, as evidenced by the persistence of a normal nucleotide pattern. However, at an air temperature of 30°C, the fall in muscle temperature is prevented, and muscle chemistry then indicates inadequate oxygen supply. 

Animal studies show that the barbiturates are metabolized in the liver, more especially in the smooth surfaced, lightest density microsomes. The enzyme systems involved require both reduced triphosphopyridine nucleotide and oxygen (14). The kidneys also metabolize certain other barbiturates, enzymetrically to a limited extent, but their role in this respect is far less than the liver. The brain, muscle, and other tissues may also to a very limited extent metabolize these agents. 

The concentration of ATP in many types of healthy cells is 5 mM, while the concentration of ADP is much less at 0.2 mM AMP concentrations are typically 1 xM. The ratios of the concentrations of these adenine nucleotides are important in the control of metabolic processes. Except under extreme circumstances such as very fatigued muscle, the total concentration of the adenine nucleotide pool remains constant at 5 mM. The constancy of the total amount of recycled metabolites such as ATP is referred to as moiety conservation cells do this on time scales of hours to days. 

Reichmann, H. DeVivo, D.C. (1991) Comp. Biochem. Physiol. 98R 327-331. Coordinate enzymatic activity of beta-oxidation and purine nucleotide cycle in a diversity of muscle and other organs of rat. Melde, K., Jackson, S., Bartlett, K., Sherratt, H.S.A. Ghisla, S. 99 )Biochem. J. 274,395-400. Metabolic consequences of methylenecyclopropylglycine poisoning in rats. 

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). 

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... 

The regulation of mammalian adenylosuccinate synthetase is complicated. It is dependent on the isozyme content and levels in a given tissue as well as the effects of substrate and product levels. The two isozymes may have different metabolic roles either in AMP biosynthesis and interconversion, or in the functions of the purine nucleotide cycle. Most studies have considered kinetic parameters for the isolated enzyme and in only a few instances has regulation been studied in vivo. Sufficient information is available concerning the regulation of the basic isozyme in muscle to consider that enzyme in detail. Factors controlling the acidic isozyme are less clearly defined. 

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