Nucleotides, uridine

Uracil, uridine and uridine nucleotides. Resolved by ion-exchange chromatography AGl (Cl form). [Lindsay et al. Anal Biochem 24 506 7968.]... 

The terms first, second, and third nucleotide refer to the individual nucleotides of a triplet codon. U, uridine nucleotide C, cytosine nucleotide A, adenine nucleotide G, guanine nucleotide Term, chain terminator codon. AUG, which codes for Met, serves as the initiator codon in mammalian cells and encodes for internal methionines in a protein. (Abbreviations of amino acids are explained in Chapter 3.)... 

UDP and UTP are selective agonists of certain of the P2Y receptors. It is not yet clear what factors control the release of uridine nucleotides into the extracellular space. UTP can be formed from UDP in the extracellular space by the action of the enzyme nucleoside diphosphokinase, which catalyzes the transfer of the -phosphate of nucleoside triphosphates to nucleoside diphosphates, e.g., ATP + UDP —> ADP + UTP. 

P2Y receptors are activated by adenine and uridine nucleotides. Most of the known P2Y receptors have been detected in the nervous system [21]. The majority of P2Y receptors inhibit neuronal N-type Ca2+ channels and M-type K+ channels. P2Y1 receptors are found exclusively on platelets, on their precursor megakaryocyte cells and on certain other cultured hematopoietic cells, such as K562 leukemia cells. They can be distinguished from other P2 receptors in that ADP is the most potent natural agonist and ATP is a competitive antagonist. ADP acts via a G protein to inhibit cyclic AMP accumulation, mobilize intracellular Ca2+ and stimulate granule secretion. ADP... 

Most eukaryotic mRNA molecules have up to 250 adenine bases at their 3 end. These poly (A) tails can be used in the affinity chromatographic purification of mRNA from a total cellular RNA extract. Under high salt conditions, poly (A) will hybridize to oligo-dT-cellulose or poly(U)-sepharose. These materials are polymers of 10 to 20 deoxythymidine or uridine nucleotides covalently bound to a carbohydrate support. They bind mRNA containing poly (A) tails as short as 20 residues. rRNA and tRNA do not possess poly (A) sequences and will not bind. After washing the mRNA can be eluted with a low salt buffer. 

The fact that many agents which interrupt the synthesis of pyrimidine nucleotides from orotic acid in animals can also inhibit the growth of experimental neoplasms suggests a search for additional antimetabolites whose locus of action is in this metabolic sequence. Two in vitro biological screening systems were developed for this purpose [202—207]. From a study of systems with oxidative energy sources, 5-bromo-[208—209] (Villa), 5-chloro-[210] (Vlllb) and 5-diazo-orotic acid [211] (IX) were found to inhibit the conversion of orotic acid to the uridine nucleotides by 40—100 per cent [202]. 

Ethyl 2-ethylthio-4-chloro-5-pyrimidinecarboxylate (XXIIa), as well as the corresponding4-hydroxy-(XXIIb) and 4-amino-(XXIIIa) derivatives, possess-anti-cytogenic activity on Neurospora crassa [223, 224]. Compounds (XXIIIa, b and c) were found to inhibit the conversion of orotic acid to the uridine nucleotides [202]. Ethyl 2-methylthio-4-(halo-substituted anilino)-5-pyrimidinecarboxylates (XXIV), particularly the o-bromo- and the o-chloro- derivatives, substantially inhibit the growth of five experimental mouse tumours (Krebs-2 ascites carcinoma, Ehrlich carcinoma clone 2, leukaemia L-1210, carcinoma 755 and lymphocytic neoplasm P-288) [225]. Compounds of this type are usually prepared by the base catalysed condensation of ethoxymethylenemalonic esters or related derivatives with urea, thiourea, guanidine, or substituted amidine-type analogues [212, 225-237]. 

B. Galactose and glucose are converted to uridine nucleotides and ultimately inter-... 

The rapid and extensive depletion of UTP is thought to be the basic cause of the toxicity. Galactosamine combines with UDP to form UDP-galactosamine (Fig. 7.62), which sequesters UDP, and therefore does not allow cycling of uridine nucleotides. Consequently, synthesis of RNA and hence protein are depressed, and sugar and mucopolysaccharide metabolism are disrupted. The latter effects may possibly explain the membrane damage that occurs. The toxic effects of galactosamine can be alleviated by the administration of UTP or its precursors. 

Phosphorylation of dCDP to dCTP (step k, Fig. 25-14) completes the biosynthesis of the first of the pyrimidine precursors of DNA. The uridine nucleotides arise in two ways. Reduction of UDP yields dUDP (step), Fig. 25-14). However, the deoxycytidine nucleotides are more often hydrolytically deaminated (reactions / and / ) 274 Methylation of dUMP to form thymidylate, dTMP (step n, Fig. 25-14), is catalyzed by thymidylate synthase. The reaction involves transfer of a 1-carbon unit from methylene tetrahydrofolic acid with subsequent reduction using THF as the electron donor. A probable mechanism is shown in Fig. 15-21. See also Box 15-E. Some bacterial transfer RNAs contain 4-thiouridine (Fig. 5-33). The sulfur atom is introduced by a sulfurtransferase (the Thil gene product in E. coli). The same protein is essential for thiamin biosynthesis (Fig. 25-21)274a... 

Leloir discovered the role of uridine nucleotides in carbohydrate metabolism. 

J. L. Strominger, Symposium on Uridine Nucleotides, Proc. Intern. Congr. Biochem., Srd Congr. Brussels, 19BB, 165 (1956). 

The peptides in the accumulated uridine nucleotides from another penicillin-inhibited strain of Staphylococcus aureus have been shown - to contain alanine, glycine, lysine, aspartic acid, and glutamic acid in various combinations. The most complex peptide contained alanine, lysine, glycine, glutamic acid, and aspartic acid in the ratios 2 2 2 1 1. All of these amino acids were present in hydrolyzates from the bacterial cell-wall of the strain. 

The presence of uridine 5-(D-glucosyluronic acid dihydrogen pyrophosphate) in both pneumococci indicates that this compound mediates the transfer of n-glucuronic acid to n-glucose (as the acceptor), giving rise to the repeating disaccharide unit of the capsular polysaccharide. The isolation of identical uridine nucleotides from both types indicates that the failure of the Type-II strain to produce capsular polysaccharide resides in a subsequent conjugation step or an even later polymerization step. 

With hyaluronic acid, much of the informative work on its biosynthesis has accrued from studies with bacteria. Group A hemolytic streptococci have long been known (K6) to produce hyaluronic acid identical with that present in mammalian connective tissues. The participation of uridine nucleotides in the biosynthesis of hyaluronic acid is now well... 

Synthesis of thymidyiate requires uridine nucleotide to be converted to the deoxy form. The substrate for Thymidyiate Synthetase is dUMP, the ] J5 jsjio. methylene-tetrahydrofolate (CH3-THF) is the "methyl" donor. This form of folate derives its carbon from serine ... 

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