Cytosine triphosphate CTP

A plot of VQ against [S] for an allosteric enzyme gives a sigmoidal-shaped curve. Allosteric enzymes often have more than one active site which co-operatively bind substrate molecules, such that the binding of substrate at one active site induces a conformational change in the enzyme that alters the affinity of the other active sites for substrate. Allosteric enzymes are often multi-subunit proteins, with an active site on each subunit. In addition, allosteric enzymes may be controlled by effector molecules (activators or inhibitors) that bind to a site other than the active site and alter the rate of enzyme activity. Aspartate transcarbamoylase is an allosteric enzyme that catalyzes the committed step in pyrimidine biosynthesis. This enzyme consists of six catalytic subunits each with an active site and six regulatory subunits to which the allosteric effectors cytosine triphosphate (CTP) and ATP bind. Aspartate transcarbamoylase is feedback-inhibited by the end-product of the pathway, CTP, which acts as an allosteric inhibitor. In contrast, ATP an intermediate earlier in the pathway, acts as an allosteric activator. 

EC 2.7.1.33) to N-(i )-4 -phosphopantothenate. Activation of the carboxylate results from the addition of P-alanine (P-alanine is formed on decarboxylation of aspartate [Asp, D], EC 4.1.1.11), by cytidylate formation (cytosine triphosphate [CTP] is followed by coupling to L-cysteine (Cys, C) (EC 6.3.2.S) to produce N-[(i )-4 -phosphopantothienoyl]-L-< steine. Oxidation to the thioaldehyde with flavin mononucleotide (EMN FMNH2) allows decarboxylation of the latter with the formation of the corresponding enol. Then, reduction with nicotinamide adenine dinucleotide phosphate (NADPH/IT NADP) (EC 4.1.1.36) leads to 4-phosphopantetheine (pantetheine 4 -phosphate). 

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. 

Cytosine Cytidine Cytidylic add Cytidine monophosphate (CMP) Cytidine diphosphate (CDP) Cytidine triphosphate (CTP)... 

This is the first step of the pathway that leads to the formation of cytosine, a building block for DNA synthesis. The form of cytosine that is used to synthesize DNA (and RNA) is the molecule cytidine triphosphate (CTP). When intracellular CTP concentrations are high, CTP molecules bind more often to the allosteric sites on aspartate transcarbamoylase molecules, causing a change in the shape of the enzyme that slows reaction 1 down markedly. Thus, CTP is an allosteric inhibitor of this enzyme. 

A major advance in the understanding of the biosynthesis of the glycerophos-phatides was the discovery by Kennedy and Weiss (1956) of the role of nucleotides of cytosine in the biosynthesis of the glycerophosphatides. Cytidine 5 -triphosphate (CTP) was shown to be necessary for the incorporation of phosphorylcholine into lecithin by liver preparations. Similar observations have been reported for brain (McMubbay et al. 1957, Stbickland et al. 1963) and other tissues. The nucleotide requirement is specific for CTP, none of the other nucleoside 5 -triphosphates being active. Kennedy and Weiss (1956) showed that CTP combines with phosphorylcholine to form the intermediate CDP-choline (IV) according to the equation ... 

Figure 12 Gradient separation of bases, nucleosides and nucleoside mono- and polyphosphates. Column 0.6 x 45 cm. Aminex A-14 (20 3 p) in the chloride form. Eluent 0.1 M 2-methyl-2-amino-l-propanol delivered in a gradient from pH 9.9-100 mM NaCl to pH 10.0-400 mM NaCl. Flow rate 100 ml/hr. Temperature 55°C. Detection UV at 254 nm. Abbreviations (Cyt) cytosine, (Cyd) cytidine, (Ado) adenosine, (Urd) uridine, (Thyd) thymidine, (Ura) uracil, (CMP) cytidine monophosphate, (Gua) guanine, (Guo) guanosine, (Xan) xanthine, (Hyp) hypoxanthine, (Ino) inosine, (Ade) adenosine, (UMP) uridine monophosphate, (CDP) cytidine diphosphate, (AMP) adenosine monophosphate, (GMP) guanosine monophosphate, (IMP) inosine monophosphate, (CTP) cytidine triphosphate, (ADP) adenosine diphosphate, (UDP) uridine monophosphate, (GDP) guanosine diphosphate, (UTP) uridine triphosphate, (ATP) adenosine triphosphate, (GTP), guanosine triphosphate. (Reproduced with permission of Elsevier Science from Floridi, A., Palmerini, C. A., and Fini, C., /. Chromatogr., 138, 203, 1977.)...

The production of CTP by amination of UTP. The conversion of the pyrimidine ring of uracil to cytosine occurs at the level of the nucleotide triphosphate. The enzyme responsible for this conversion is known as cytidine triphosphate synthase. 

Site of action Like the other purine and pyrimidine antagonists, ara-C must be sequentially phosphorylated to the corresponding nucleotide, cytosine arabinoside triphosphate (ara-CTP), in order to be cytotoxic. It is S-phase (hence cell-cycle) specific. Ara-C is also incorporated into DNA and can terminate chain elongation. It can also inhibit the reduction of CDP to dCDP. 

Despite these similarities, there are some very important differences between the reactions carried out by DNA polymerase and RNA polymerase. Remember that DNA is synthesized with the use of four deoxyn bon ucl cosidc triphosphates (dATP, dGTP, dTTP, and dCTP). In the double-stranded DNA helix, adenine bases hydrogen-bond with thymine bases, and guanine bases hydrogen-bond with cytosine bases. RNA, however, is synthesized with the use of four ribonucleoside triphosphates (ATP, GTP, CTP, and UTP). Adenine and guanine bases in the DNA template will direct the addition of uracil and cytosine bases to the growing RNA molecule, respectively, while... 

Cytarabine (ara-C) is an arabinose analog of cytosine. Cytarabine was originally isolated from sponges, but is now produced synthetically. Ara-C is phosphorylated to its active triphosphate form (ara-CTP) within tumor cells. Ara-CTP inhibits DNA polymerase, an enzyme responsible for strand elongation. It is also incorporated directly into DNA, where it inhibits the replication of DNA and acts as a chain terminator to prevent DNA elongation. Activation of ara-C is opposed by deaminase enzymes, particularly cytidine deaminase, which degrades ara-C to an inactive form, ara-U. " " ... 

RNA polymerase is an enzyme that makes RNA using DNA as a template. RNA polymerase uses the nucleoside triphosphates, ATP, GTP, CTP, and UTP (uridine triphosphate) to make RNA. The nucleoside bases adenine, guanine, cytosine and uracil pair with the bases thymine, cytosine, guanine, and adenine, respectively, in DNA to make RNA. Like DNA polymerase (see here), RNA polymerases catalyze polymerization of nucleotides only in the 5 to 3 direction. Unlike DNA polymerases, however, RNA polymerases do not require a primer to initiate synthesis. 

From this point, MEP is coupled to cytidine triphosphate to produce 4-diphosphocytidyl-2C-methyl-D-erythritol (CDP-ME) in a reaction, which is catalyzed by 4-diphospho-cytidyl-2C-methyl-D-erythritol transferase (IspD) [2.7.7.60] (Scheme 5.2). IspD structure-mechanism analysis showed that a sequential mechanism applies with a Mg ion coordinating first, followed by CTP binding and then MEP [22]. The cytosine base portion of the substrate or the product is hydrogen bonded to Ala 14, Alai 5, Gly82, Asp 83, and Sep88 based on smdies conducted on product-bound cocrystal of IspD from E. coli [23]. 

Figure 10 Chemical structures of adenosine 5 -monophosphate (n = 1 AMP ), adenosine 5 -diphosphate (n = 2 ADP "), and adenosine 5 -triphosphate (n = 3 ATP ) as well as of cytidine 5 -monophosphate (n = 1 CMP, cytidine 5 -diphosphate (n = 2 CDP ), and cytidine 5 -triphosphate (n = 3 CTP ) in their dominating anti conformation [11-14,50]. Note, the triphosphate chain in nucleoside 5 -triphosphates (NTP ) is labeled a, P, and y, where y refers to the terminal phosphate group (see also Figure 9) for nucleoside 5 -diphosphates (NDP ) the situation is analogous with a and P (see Figure 9). The adenine and cytosine residues in the nucleotide structures shown above may be replaced by one of the other nucleobase residues shown in Figiue 1 if this substitution is done in the way the bases are depicted within the plane (Figure 1), then the anti conformation will also result for the corresponding nucleoside 5 -phosphates. The abbreviations AMP, ADP , ATP , IMP, etc. in this text always represent the 5 -derivatives 2 - and 3 -derivatives are defined by 2 AMP, 3 AMP, etc. in a few instances where uncertainties might otherwise occur, the abbreviations 5 AMP , 5 ADP , etc. are also used.

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