Muscle adenylate kinase

In the preceding sections the conversion of purines and purine nucleosides to purine nucleoside monophosphates has been discussed. The monophosphates of adenosine and guanosine must be converted to their di- and triphosphates for polymerization to RNA, for reduction to 2 -deoxyribonucleoside diphosphates, and for the many other reactions in which they take part. Adenosine triphosphate is produced by oxidative phosphorylation and by transfer of phosphate from 1,3-diphosphoglycerate and phosphopyruvate to adenosine diphosphate. A series of transphosphorylations distributes phosphate from adenosine triphosphate to all of the other nucleotides. Two classes of enzymes, termed nucleoside mono-phosphokinases and nucleoside diphosphokinases, catalyse the formation of the nucleoside di- and triphosphates by the transfer of the terminal phosphoryl group from adenosine triphosphate. Muscle adenylate kinase (myokinase)... 

Kuby, S.A. Hamada, M. Gerber, D. Tsai, W.-C. Jacobs, H.K. Cress, M.C. Chua, G.K. Fleming, G. Wu, L.H. Fischer, A.H. Frischat, A. Maland, L. Studies on adenosine triphosphate transphosphorylases. Isolation and several properties of the crystalline calf ATP-AMP transphosphorylases (adenylate kinases) from muscle and liver and some observations on the rabbit muscle adenylate kinase. Arch. Biochem. Biophys., 187, 34-52 (1978)... 

Purich, D.L. Fromm, H.J. Inhibition of rabbit skeletal muscle adenylate kinase by the transition state analogue, P P -di(adenosine-5 )tetraphos-phate. Biochim. Biophys. Acta, 276, 563-567 (1972)... 

Li, X. Pan, X.M. Both native conformers of rabbit muscle adenylate kinase are active. FEBS Lett., 480, 235-238 (2000)... 

Sheng, X. Pan, X. Wang, C. Zhang, Y. Jing, G. Conformational and functional significance of residue proline 17 in chicken muscle adenylate kinase. FEBS Lett., 508, 318-322 (2001)... 

Creatine kinase was purified from rabbit muscle by the method of Kuby et al, (4). Rabbit muscle pyruvate kinase was purchased from Boehringer. Porcine muscle adenylate kinase was purchased from Sigma, and was further purified by gel filtration on Sephadex G-50. The enzymes were homogeneous as judged by their specific activities and by their migration as single components in sodium dodecyl sulfate gel electrophoresis. Proton NMR spectra at 250 MHz of 0.5-2.0 mM enzyme sites in 0 solution were obtained with a Bruker WM 250 MHz pulse FT spectrometer at 25°. At least 256 transients were accumulated over 8192 data points using 16 bit A/D conversion. Relaxation rates and histidine pK values were determined by standard NMR methods (5, 6),... 

Parallel enzymes in two mammalian species can be analogous instead of (as expected) identical. For instance, rabbit muscle adenylate kinase is inactivated by 0.8 mM A -iodoacetamidohexyladenosine 5 -phosphate, whereas the corresponding enzyme in pig muscle was quite unaffected even by a 2.8 mM solution (Hampton, 1976). 

Recently, Rhoads and Lowenstein (6) have utilized initial velocity and equilibrium kinetics to study the kinetic mechanism of muscle adenylate kinase from rabbit muscle and have concluded that the reaction is of the random bi-bi type. Isotope exchange between adenylate and ADP is... 

The two sulfhydryl groups of muscle adenylate kinase are not involved in substrate binding, although the enzyme may be reversibly inactivated with sulfhydryl reagents (7, 8). 

Muscle Adenylic Kinase. This unusual enzyme catalyzes the reaction 2ADP ATP - - AMP. It is a heat-stable, acid-stable enzyme, requiring Mg++ for maximum activity. It is specific for the adenine nucleotides and reaches an equilibrium when two-thirds of the added ADP has been converted to the mixture of AMP and ATP. Since the discovery of this enzyme, systems catalyzing the same reaction but consisting... 

Adenylate kinase (AK) is a ubiquitous monomeric enzyme that catalyzes the interconversion of AMP, ADP, and ATP. This interconversion of the adenine nucleotides seems to be of particular importance in regulating the equilibrium of adenine nucleotides in tissues, especially in red blood cells. AK has three isozymes (AK 1,2, and 3). AK 1 is present in the cytosol of skeletal muscle, brain, and red blood cells, and AK 2 is found in the intermembrane space of mitochondria of liver, kidney, spleen, and heart. AK 3, also called GTP AMP phosphotransferase, exists in the mitochondrial matrix of liver and heart. 

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. 

Schirmer, R.H. Thuma, E. Sensitivity of adenylate kinase isozymes from normal and dystrophic human muscle to sulfhydryl reagents. Biochim. Biophys. Acta, 268, 92-97 (1972)... 

Kurebayashi, N. Kodama, T. Ogawa, Y. P p5-Di(adenosine-5 )pentaphos-phate(Ap5A) as an inhibitor of adenylate kinase in studies of fragmented sarcoplasmic reticulum from bullfrog skeletal muscle. J. Biochem., 88, 871-876 (1980)... 

Tamura, T. Shiraki, H. Nakagawa, H. Purification and characterization of adenylate kinase isozymes from rat muscle and liver. Biochim. Biophys. Acta, 612, 56-66 (1980)... 

Phosphoryl group transfers from ATP result in an accumulation of ADP for example, when muscle is contracting vigorously, ADP accumulates and interferes with ATP-dependent contraction. During periods of intense demand for ATP, the cell lowers the ADP concentration, and at the same time acquires ATP, by the action of adenylate kinase ... 

AMP concentration is a much more sensitive indicator of a cell s energetic state than is ATP. Normally cells have a far higher concentration of ATP (5 to 10 mM) than of AMP (<0.1 mM). When some process (say, muscle contraction) consumes ATP, AMP is produced in two steps. First, hydrolysis of ATP produces ADP, then the reaction catalyzed by adenylate kinase produces AMP ... 

Nucleoside diphosphates (NDP) are synthesized from the corresponding nucleoside monophosphates (NMP) by base-specific nucleoside monophosphate kinases (Figure 22.9). [Note These kinases do not discriminate between ribose or deoxyribose in the substrate.] ATP is generally the source of the transferred phosphate, because it is present in higher concentrations than the other nucleoside triphosphates. Adenylate kinase is particularly active in liver and muscle, where the turnover of energy from ATP is high. Its function is to maintain an equilibrium among AMP, ADP, and ATP. Nucleoside diphosphates and triphosphates are interconverted by nucleoside diphosphate kinase—an enzyme that, unlike the monophosphate kinases, has broad specificity. 

Thermal tolerance of isolated muscle tissue and of proteins, such as adenylate kinase and actomyosin, of small and large varieties of Black Sea horse-mackerel has been studied by Altukhov (1962) and Glushankova (1967). Johnston et al. (1973) focused on determining the thermoresistance of ATPase... 

Savina, 1992). Moreover, as these authors and Silkina (1990) note, the white muscle of sluggish fish often exceeds that of highly active species in the characteristics described above. This thesis is supported by the data of Emeretli (1990) on LDH and ATPase activity measured in the muscles of horse-mackerel and scorpion fish (Figure 17). The creatine- and adenylate kinase reactions in the white muscle of sluggish fish appear to proceed at a greater rate than in more... 

Mitochondrial oxidative ADP phosphorylation is the primary source of ATP in skeletal muscle during aerobic exercise. Thus, to maintain the tree-energy state of the cytoplasmic phosphoenergetic compounds ATP, ADP, and inorganic phosphate (PI), oxidative phosphorylation is modulated to match the rate of ATP utilization during exercise. The mitochondrial components of Wu et a/. s model are illustrated in Figure 7.13. Additional components include ATP hydrolysis, adenylate kinase,... 

Phosphorylation by ADP, catalyzed by adenylate kinase - this enzyme is especially important in the rapid synthesis and turnover of thiamin triphosphate in slow-twitch white muscle fibers. 

Miyamoto T, Kakizawa T, and Hashizume K (1999) Inhibition of nuclear receptor signalling by poly(ADP-ribose) polymerase. Molecular and Cell Biology 19,2644-9. Miyoshi K, Egi Y, Shioda T, and Kawasaki T (1990) Evidence for in vivo synthesis of thiamin triphosphate by cytosolic adenylate kinase in chicken skeletal muscle./oMrnal... 

In muscle contraction, ATP is converted into ADP. Adenylate kinase converts two molecules of ADP into a molecule of ATP and AMP. 

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