Inosine triphosphate

Ap4A, diadenosine tetraphosphate BBG, Brilliant blue green BzATP, 2 - 3 -0-(4-benzoyl-benzoyl)-ATP cAMP, cyclic AMP CCPA, chlorocyclopentyl adenosine CPA, cyclopentyl adenosine CTP, cytosine triphosphate DPCPX, 8-cyclopentyl-1,3-dipnopylxanthine IP3, inosine triphosphate lpsl, diinosine penta phosphate a,p-meATP, a,p-methylene ATP p.y-meATP, p.y-meihylene ATP 2-MeSADP, 2-methylthio ADP 2-MeSAMP, 2-methylthio AMP 2-MeSATP, 2-methylthio ATP NECA, 5 -W-ethylcarboxamido adenosine PPADS, pyridoxal-phosphate-6-azophenyl-2, 4 -disulfonic acid PLC, phospholipase C RB2, reactive blue 2 TNP-ATP, 2, 3 -0-(2,4,6-trinitrophenyl) ATP. 

By this method adenosine triphosphate (ATP) and inosine triphosphate (ITP) were prepared in 89% and 93% yield, respectively 51]... 

Fig. 13.1 Pathways of thiopurine metabolism. The positions of two polymorphically expressed enzymes, TPMT (thiopurine methyl transferase) and ITPA (inosine triphosphate pyrophosphatase), are shown. HGPRT, hypoxanthine guanine phosphoribosyl transferase 6-TIDP, 6-thioi-nosine diphosphate 6-TIMP, 6-thioinosine monophosphate 6-TITP, 6-thio inosine trinophosphate...

Inosine triphosphate pyrophosphatase (TTPA) deficiency may lead to accumulation of 6-thioinosine triphosphate (ITP) in those treated with AZA or 6-MP. The gene encoding ITPA is located on chromosome 20, and two of five single-nucleotide... 

Marinaki, A. M., Ansari, A., Duley, J. A., et al. (2004) Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). Pharmacogenetics. 14,181-187. 

Zelinkova, Z., Deiijks, L. J., Stokkers, P. C., et al. (2006) Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression. Clin. Gastroenterol. Hepatol. 4, 44-49. 

All muscarinic receptors are members of the seven transmembrane domain, G protein-coupled receptors, and they are structurally and functionally unrelated to nicotinic ACh receptors. Activation of muscarinic receptors by an agonist triggers the release of an intracellular G-protein complex that can specifically activate one or more signal transduction pathways. Fortunately, the cellular responses elicited by odd- versus even-numbered receptor subtypes can be conveniently distinguished. Activation of Ml, M3, and M5 receptors produces an inosine triphosphate (IP3) mediated release of intracellular calcium, the release of diacylglyc-erol (which can activate protein kinase C), and stimulation of adenylyl cyclase. These receptors are primarily responsible for activating calcium-dependent responses, such as secretion by glands and the contraction of smooth muscle. 

NMDA, Af-methyl-D-aspartate AMPA, a-amino-3-hydroxy-5-methyl-isoxazole-4-proprionic add 1S,3R-ACPD, L-amino-cydopentane-lS,3R-dicarboxylic add IP3, inosine triphosphate... 

In animals and in many bacteria, PEP is formed by decarboxylation of oxaloacetate. In this reaction, which is catalyzed by PEP carboxykinase (PEPCK), a molecule of GTP, ATP, or inosine triphosphate captures and phosphorylates the enolate anion generated by the decarboxylation (Eq. 13-46).252 The stereochemistry is such that C02 departs from the si face of the forming enol.253 The phospho group is transferred from GTP with inversion at the phosphorus atom 254 The enzyme requires a divalent metal ion, preferably Mn2+. 

Hypoxanthine Ribose Inosine Inosinic acid inosine monophosphate (IMP) Inosine diphosphate (IDP) Inosine triphosphate (ITP)... 

The interaction of certain members of the G protein family with an enzymatic activity known as phospholipase C results in the hydrolysis of the membrane phospholipid, phosphatidyl inositol, into diacylglycerol (DAG) and inosine triphosphate (IP3) shown in Fig. 4.9C (Ross, 1992a Kennedy, 1992 Hardie, 1991). DAG is an activator of the protein kinase C family of enzymes discussed below, and acts by reducing the level of calcium needed for their activation. (Several diacylglycerols, depending on the exact... 

IP3 inositol 1,4,5,-trisphosphate ITP inosine triphosphate LDL low-density lipoprotein Leu leucine Lys lysine Met methionine... 

Shipkova M, Franz J, Abe M, Klett C, Wieland E, Andus T (2011) Association between adverse effects under azathioprine therapy and inosine triphosphate pyrophosphatase activity in patients with chronic inflammatory bowel disease. Ther Drug Monit 33 321-328... 

Stocco G, Cheok MH, Crews KRet al (2009) Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia. Clin Pharmacol Ther 85 164-172... 

Fig. 2 Metabolism of 6-mercaptopurine (6-MP) via xanthine oxidase (XO) to the inactive metabolite 6-thiouric acid (6-TU), thiopurine S-methyltransferase (TPMT) to the inactive metabolite 6-methylmercaptopurine (6-MMP), and hypoxanthine guanine phosphoribosyl transferase (HPRT) to 6-thioinosine monophosphate (6-TIMP) which is then further metabolized to thioguanine nucleotides (6-TGN), 6-methylmercaptopurine ribonucleotides (6-MMPR) or 6-thio-inosine triphosphate (6-thio-ITP), these all being active metabolites...

In this reaction, inosine triphosphate (ITP) can substitute for guanosine triphosphate (GTP), and the CO2 lost is the one fixed in the carboxylase reaction. The net result of these reactions is... 

Japan, pat. 732C86) (to Ajinomoto), C.A. 51, 3870b (1957). Structure Levene, Bess, op. ctt.. pp 187-192 Bredereck, Ber. 66, 198 (1933) Levene, Tipson, J. Biol. Chem. Ill, 3t3 (1935). Also prepd from muscle by enzymatic deamination of muscle adenylic acid Ostem, Biochem. Z. 254, 63 (1932) by hydrolysis of inosine triphosphate Kleinzeller, Biochem. J. 36, 729 (1942). Studies on the enzymatic synthesis Greenberg, J. Biol. Chem. 198, 611 (1951) Korn et al, ibid 217, 875 (1955). Microbial fermentation method using mutant strains of Micrococcus glutamicus Kinoshita el al. U.S. pat. 3,232,844 (1966 to Kyowa). 

The present review will deal with the properties of these five systems and their behavior on the addition of adenosine triphosphate (ATP), adenosine diphosphate (ADP), inosine triphosphate (ITP), inorganic triphosphate, and pyrophosphate. The really important question is how far the interaction phenomena with ATP can be regarded as a model for contraction in living muscle—a model for contraction as a whole in the case of the earlier of these stages, and a model of the molecular mechanism in the case of the later stages. For the relaxation phase, no model is yet known (c/. however. Section II, Ah and appendix). 

This enzyme activity has been observed in myosin and actomyosin, mitochondria, microsomes, and cell membranes. In some cases magnesium ions function as an activator, in others calcium ions, and in still others, both calcium and magnesium are requited. Another form of adenosine-triphosphatase is stimulated by sodium and potassium ions and is inhibited by ouabain. Some forms of the enzyme can hydrolyse inosine triphosphate and other nucleoside-5 -triphosphates. The substrate specificity may depend upon the activating divalent cation and on the presence of monovalent cations. These enzymes are probably important components of a system responsible for facilitating cation transfer in membranes. They should not be confused with adenosine triphosphate pyrophosphatase E.C. 3.6.1.8. 

Other nucleoside triphosphates, which are energetically equivalent to ATP, are important in some metabolic reactions cytidine triphosphate in phospholipid biosynthesis, guanosine triphosphate in protein biosynthesis and oxidative decarboxylation of 2-oxoacids (see Thcarboxylic acid cycle), inosine triphosphate in certain carboxylations, uridine triphosphate in polysaccharide biosythesis. 

Acyl adenylate intermediates seem the general rule for acyl activation, but alternate mechanisms are known. An example is the succinyl thio-kinase reaction. The mammalian enzyme system utilizes guanosine triphosphate (GTP) or inosine triphosphate (ITP), although similar ATP-requiring enzymes are known from plants and bacteria. In addition to the coenzyme A derivative, a nucleoside disphosphate and inorganic phosphate are produced. 

Figure 1 The metabolism of azathioprine and mercaptopurine Key AO, aldehyde ojddase GMPS, guanine monophosphate synthetase HPRT, hypoxanthine phosphoribosyl transferase IMPDH, inosine monophosphate dehydrogenase ITPA, inosine triphosphate pyrophosphohydrolase TPMT, thiopurine methyltransfer-ase XO/XDH, xanthine oxidase/dehydrogenase.

Xiong H, Xin HW, Wu XC, Li Q, Xiong L, Yu AR. Association between inosine triphosphate pyrophosphohydro-lase deficiency and azathioprine-related adverse drug reactions in the Chinese kidney transplant recipients. Fundam Clin Pharmacol 2010 24(3) 393-400. 

Triphosphate Inosine 5 -(tetrahydrogen triphosphate). Inosine triphosphate. FTP [132-06-9]... 

The steps required to convert mevalonic acid to the active-isoprenoid intermediate have been worked out with some assurance. The initial step involves the phosphorylation of mevalonic acid to mevalonic acid-5-phosphate by an enzyme called mevalonic kinase. This enzyme was found in yeast by Tchen (1958). The properties of the mevalonic kinase of liver have been described in detail by Levy and PopjAK (1960). The kinase is inhibited by p-chloromercuribenzoate but not by iodoacetamide. The enzyme requires Mg++, Mn++, or Ca++ and ATP or inosine triphosphate. The kinase is specific for the (+) form of mevalonic acid. Mevalonic acid-5-phosphate is phosphorylated further to give mevalonic acid-5-pyrophos-phate (de Waard and Popjak, 1959 Henning et al. 1959). The purified enzyme (Bloch et al., 1959) requires a divalent metal ion for activity (Mg++ is preferable) and has no pronounced pH optimum. Mevalonic acid pyrophosphate then undergoes simultaneous dehydration and decarboxylation to yield isopentenylpyro-phosphate (Lynen et al., 1958 Chaykin et al., 1958). The enzyme concerned with the dehydration and decarboxylation has been purified (Bloch et al., 1959) and shown to have a pH optimum between 5.5 and 7.4 and to require a divalent metal ion (Mg++, Mn++, Fe++ or Co++). The series of reactions in which mevalonate is converted to isopentenylpyrophosphate is outlined in Figure 6. Brodie et al. (1963) have established a new pathway for the biosynthesis of mevalonic acid from malonyl CoA. The importance of this particular pathway in the synthesis of sterols is still unknown. 

There are at least three enzymes which will hydrolyze adenosine triphosphate. Myosin, one of the active proteins of muscle, has very strongly associated with it an adenosinetriphosphatase which is activated by calcium ions and inhibited by magnesium. Cleavage of only the terminal phosphate of ATP occurs, and inosine triphosphate is the only other substrate attacked. Not associated with myosin is a water-soluble adenosinetriphosphatase described by Kielley and Meyerhof. It is strongly... 

ADA is involved in an important step in purine salvage by converting adenosine to inosine. ADA deficient erythrocytes accumulate adenosine triphosphate and convert inosine monophosphate to inosine triphosphate at an increased rate. The accumulation of adenosine or another product in these infants may be lymphocytotoxic or interfere with pyrimidine biosynthesis by... 

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