Cytidine 5 -triphosphate

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.)...

Angle CR, Mclntire MS, Swanson MS, et al. 1982. Erythrocyte nucleotides in children—increased blood lead and cytidine triphosphate. Pediatr Res 16 331-334. 

ATCase catalyzes the first step in the biosynthesis of cytidine triphosphate (CTP). The sequence of reactions leading from the reactants, aspartate and carbamoyl phosphate, to CTP is shown in Fig. 8.19. 

Figure 8.19. Sequence reactions from aspartic acid (AA) and carbamoyl phosphate (CP) to the end product, cytidine triphosphate (CTP). The first reaction is catalyzed by ATCase. The intermediary compounds are N-carbamoyl aspartic acid (N-CAA), L-dihydroorotic acid (L-DHOA), orotic acid (OA), orotidine 5 -phosphate (0-5 -P), uridine 5 -phosphate (U-5 -P), uridine diphosphate (UDP), and uridine triphosphate (UTP).

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

It was snbseqnently discovered that the first enzyme in the pathway for isoleucine synthesis, which is threonine deaminase, was inhibited by isoleucine in an extract of E. coli. No other amino acid caused inhibition of the enzyme. Threonine deaminase is, in fact, the rate-limiting enzyme in the pathway for isoleucine synthesis, so that this was interpreted as a feedback control mechanism (Fignre 3.13(a)). Similarly it was shown that the hrst enzyme in the pathway for cytidine triphosphate synthesis, which is aspartate transcarbamoylase, was inhibited by cytidine triphosphate (Fignre 3.13(b)). Since the chemical structures of isoleucine and threonine, or cytidine triphosphate and aspartate, are completely different, the qnestion arose, how does isolencine or cytidine triphosphate inhibit its respective enzyme The answer was provided in 1963, by Monod, Changenx Jacob. 

Figure 3.13 (a) Feedback control of a hypothetical pathway. (b) Feedback control of threonine deaminase in the isoleucine synthetic pathway and of aspartate carbamoyltransferase in the cytidine triphosphate synthetic pathway in the bacterium E. coli. 

Phosphocholine reacts with a nucleoside triphosphate (cytidine triphosphate) in a reaction, catalysed by cholinephosphate cytidylyltransferase, which produces cytidine diphosphochoUne ... 

Figure 20.9 The positions in the pathway for de novo pyrimidine nucleotide synthesis where GLUCOSE provides the ribose molecule and GLUTAMINE provides nitrogen atoms. Glucose forms ribose 5-phosphate, via the pentose phosphate pathway (see chapter 6), which enters the pathway, after phosphorylation, as 5-phospho-ribosyl 1-pyrophosphate. Glutamine provides the nitrogen atom to synthesise carbamoylphos-phate (with formation of glutamate), and also to form cytidine triphosphate (CTP) from uridine triphosphate (UTP), catalysed by the enzyme CTP synthetase. It is the amide nitrogen of glutamine that is the nitrogen atom that is provided in these reactions.

ACTase catalyzes the transfer of a carbamoyl residue from carbamoyl phosphate to the amino group of L-aspartate. The N-carbamoyl L-aspartate formed in this way already contains all of the atoms of the later pyrimidine ring (see p. 188). The ACTase of the bacterium Escherichia coli is inhibited by cytidine triphosphate (CTP), an end product of the anabolic metabolism of pyrimidines, and is activated by the precursor ATP. 

Mutation of one of the two enzyme activities of UMP synthase leads to orotic aciduria, characterized by accumulation of its first substrate orotic acid and insufficient levels of the product UMP, which reduces availability of uridine triphosphate (UTP) and cytidine triphosphate (CTP) for use in nucleic acid synthesis. 

Cytidine triphosphate (CTP) is produced by amination of UTP by CTP synthetase (Figure 22.22). [Note The nitrogen is provided by glutamine—another example of a reaction in nucleotide biosynthesis in which this amino acid is required.]... 

Dolichyl phosphate phosphatase has been described in animal tissues,74-76 and it is possibly responsible for the free dolichol found in tissues. This free dolichol can be rephosphorylated by a dolichol kinase using cytidine triphosphate (CTP) as phosphoric donor,77-78 or acylated by a dolichol acyltransferase79 (see Scheme 1). 

Cysteine proteases 482 Cytidine deaminase 359 Cytidine triphosphate synthetase 298 Cytochrome c, folding kinetics 551... 

Molecules with structures as diverse as carbamoyl-phosphate, tryptophan, and cytidine triphosphate are feedback inhibitors of the E. coli glutamine synthase. The feedback inhibition is cumulative, with each metabolite exerting a partial inhibition on the enzyme. Why would complete inhibition of the glutamine synthase by a single metabolite be metaboli-cally unsound ... 

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. 

ADP and inorganic phosphate (fig. 23.14). Both the mammalian and bacterial cytidine triphosphate synthases can use ammonia as a donor in place of glutamine, but this reaction is of no physiological significance because the Km for ammonia is very high and the reaction rate low. 

Cytidine triphosphate is necessary to the activation of iV-acetylneuraminic acid (see Section V,3). Its preparation39-69 is given in Scheme 17. The not... 

Carbamyl-L-aspartate is the key precursor in the biosynthesis of pyrimidines. The enzyme aspartate transcarbamylase is inhibited by several pyrimidine nucleotides, notably cytidine triphosphate, and is activated by ATP, a purine nucleotide. Thus the enzyme is under feedback regulation, and controls the relative concentration of pyrimidine and purine nucleotides. 

Cytidine triphosphate Diacylglycerols and lipid head groups Bacteria, archaea and eukaryotes ... 

Some of the reactions of PO3- parallel enzymatic reactions promoted by adenosine triphosphate (ATP). Pyruvate kinase catalyzes the equilibration of ATP and pyruvate with adenosine diphosphate (ADP) and phosphoenol pyruvate (11,12). In a formal sense, this reaction resembles the preparations of enol phosphate (eqs. 6 and 7). Cytidine triphosphate synthetase catalyzes the reaction of uridine triphosphate with ammonia to yield cytidine triphosphate (13). In a formal sense, this reaction resembles the replacement of the ester carbonyl group of ethyl acetate by the nitrogen of aniline (eq. 8). 

L2. Lieberman, I., Enzymatic animation of uridine triphosphate to cytidine triphosphate. Am. Chem. Soc. 77, 2661 (1955). 

A-residue, G-residue etc. or more simply dA, dG (or A, G etc. where there is no possibility of confusion with the ribonucleotides, for example as in a DNA sequence) pdT etc. dTMP, dAMP etc. rATP, rCTP etc. A deoxyadenosine (deoxyguanosine) monophosphate either at one end, or within, a polynucleotide chain and linked to the adjacent nucleotide(s) by phosphodiester bond(s) deoxythymidine 5 -monophosphate the deoxynucleoside 3 -monophosphate the ribonudeoside triphosphates, adenosine triphosphate, cytidine triphosphate etc. 

---