Nucleotides monophosphate Guanosine

The biological chemistry of six-membered phosphorus compounds is dominated by the cyclic nucleotide monophosphates in particular, cyclic adenosine monophosphate (cAMP) [93] and cyclic guanosine monophosphate (cGMP) [94]. cAMP and cGMP play a major role in cellular communication... 

Obtain the following nucleotide standards (Sigma) adenosine-5-monophosphate uridine-5-monophosphate cytidine-5-monophosphate guanosine-5-monophos-phate. Also, obtain the following nucleoside standards (Sigma) adenosine uridine cytidine guanosine. Prepare individual standards at a concentration of 3 0,g/ Xl. 

The compounds described above may be regarded as analogs of adenosine nucleotides. The guanosine nucleotide analogs of the same group have been synthesized from 2-amino-6-mercaptopurine nucleoside using very similar procedures. A 3, 5 -cyclic monophosphate was synthesized from the 5 -monophosphate (I) after the method of Smith et aV... 

Nucleotides Separation. A method for the separation of nucleotides has been developed (10). These nucleotides include 5 -monophosphate adenosine, 5 -monophosphate cytidine, 5 -monophosphate uridine, 5 -monophosphate guanosine, and... 

In most of these reactions adenine nucleotides are employed although reactions involving nucleotides of the uridine, cytidine, and guanosine series are well known. It should be noted that nucleosides themselves and nucleotide monophosphates are surprisingly inactive in biosynthetic processes. Thus, nucleoside kinases, monophosphate kinases, and diphosphate kinases, which convert nucleoddes and nucleoside monophosphates to the di- and triphosphate stage are incUqiensable for cellular bio yntheds. 

The addition of one, two or three phosphate groups to the sugar of a nucleoside by ester linkage (alcoholic-OH + acid- ester) derives a nucleotide. The nomenclature of the nucleotide is based upon the name of the nucleoside plus the position and number of the phosphate groups, e.g. adenosine 3 -monophosphate, guanosine 5 -triphosphate. Although phosphorylation may occur at the 2, 3 or 5 positions of a ribonucleoside and at the 3 or 5 positions of a deoxyribonucleoside, the 5 -nuc-leotides are of major biological importance. 

In addition, vinpocetine selectively inhibits a specific calcium, calmodulin-dependent cycHc nucleotide phosphodiesterase (PDF) isozyme (16). As a result of this inhibition, cycHc guanosine 5 -monophosphate (GMP) levels increase. Relaxation of smooth muscle seems to be dependent on the activation of cychc GMP-dependent protein kinase (17), thus this property may account for the vasodilator activity of vinpocetine. A review of the pharmacology of vinpocetine is available (18). 

Cyclic Nucleotide-regulated Cation Channels Cyclic Guanosine Monophosphate... 

Adenylyl Cyclases Guanylyl Cyclases Transmembrane Signalling Cyclic Adenosine Monophosphate Cyclic Guanosine Monophosphate Cyclic Nucleotide-gated Channels Phosphodiesterases... 

Cyclic nucleotide phosphodiesterases (PDEs) are a class of enzymes that catalyze the hydrolysis of 3, 5 -cyclic guanosine monophosphate (cGMP) or 3, 5 -cyclic adenosine monophosphate (cAMP) to 5 -guanosine monophosphate (GMP) or 5 -adenosine monophosphate (AMP), respectively. 

The most common second messenger activated by protein/peptide hormones and catecholamines is cyclic adenosine monophosphate (cAMP). The pathway by which cAMP is formed and alters cellular function is illustrated in Figure 10.1. The process begins when the hormone binds to its receptor. These receptors are quite large and span the plasma membrane. On the cytoplasmic surface of the membrane, the receptor is associated with a G protein that serves as the transducer molecule. In other words, the G protein acts as an intermediary between the receptor and the second messengers that will alter cellular activity. These proteins are referred to as G proteins because they bind with guanosine nucleotides. In an unstimulated cell, the inactive G protein binds guanosine diphosphate (GDP). When the hormone... 

Not all analogues become active against cancer cells through incorporation into nucleic acid. Some analogues block the synthesis of normal purine and pyrimidine nucleotides for example, 8-azaguanine blocks guanosine monophosphate (GMP) synthesis and 6-mercaptopurine inhibits adenosine monophosphate (AMP) syn-thesis. 

Figure 20.10 The positions in the pathway for de novo purine nucleotide synthesis where GLUCOSE provides the ribose molecule and GLUTAMINE provides nitrogen atoms. The pathway begins with glucose which provides ribose 5-phosphate, via the pentose phosphate pathway (Chapter 6). Glutamine provides its amide nitrogen in two reactions formation of 5-phosphoribosylamine and formation of guanosine monophosphate (GMP) from xantho-sine 5-phosphate (XMP).

Mycophenolate sodium (62 Myfortic Norvatis, 2003) is an immunosuppressant drug used to prevent rejection in organ transplantation. It is a selective, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the de novo pathway of guanosine nucleotide synthesis. Thus, mycophenolic acid (61), originally... 

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)... 

Purine (left). The purine nucleotide guano-sine monophosphate (CMP, 1) is degraded in two steps—first to the guanosine and then to guanine (Gua). Guanine is converted by deamination into another purine base, xanthine. 

FIGURE 10.15 Adsorption isotherms of nucleotides on Spherisorb ODS-2 from lOOmM phosphate buffer (pH 7.0) at 25°C. ( ) Guanosine 2, 3 -cyclic monophosphate, ( ) adenosine 2, 3 -cyclic monophosphate and (A) adenosine monophosphate. (Reprinted from Huang, J.X. and Horvath, Cs., J. Chromatogr., 406, 275, 1987. With permission from Elsevier.)... 

Inhibition of cyclic nucleotide phosphodiesterases is widely accepted as the predominant mechanism by which theophylline produces bronchodilation. Phosphodiesterases are enzymes that inactivate cAMP and cyclic guanosine monophosphate (GMP), second messengers that mediate bronchial smooth muscle relaxation. 

Ribavirin is a synthetic guanosine analogue that possesses broad antiviral inhibitory activity against many viruses, including influenza A and B, parainfluenza, RS V, HCV, HIV-1, and various herpesviruses, arenaviruses, and paramyxoviruses. Its exact mechanism of action has not been fully elucidated however, it appears to inhibit the synthesis of viral mRNA through an effect on nucleotide pools. Following absorption, host cell enzymes convert ribavirin to its monophosphate, diphosphate, and triphosphate forms. Ribavirin monophosphate... 

Salt is the best known taste enhancer for a variety of foods. Monosodium glutamate (MSG) and nucleotides, such as inosine monophosphate (IMP) and guanosine monophosphate (GMP), are known to enhance flavor and are recognia as the "umami taste" in Oriental cuisine. They have longer aftertastes than the "basic... 

The most important of the aforementioned flavour-enhancing nucleotides are inosine 5 -monophosphate (IMP) and guanosine 5 -monophosphate (GMP), of which about 2,000 and 1,000 t year are produced by biotechnological processes worldwide [22] and which are used as their disodium salts. The nucleotides contribute to the flavour-enhancing effect brought into food by yeast hydrolysates. Diflerent biotechnological strategies have been developed for the production of pure nucleotides ... 

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