Nucleic acids pyrimidines

A. R. Katritzky and M. Karelson,/. Am. Chem. Soc., 113, 1561 (1991). AMI Calculations of Reaction Field Effects on the Tautomeric Equilibria of Nucleic Acid Pyrimidine and Purine Bases and Their 1-Methyl Analogues. 

The most important naturally occuring diazines are the pyrimidine bases uracil, thymine and cytosine, which are constituents of the nucleic acids (see 32.4). The nucleic acid pyrimidines are often drawn horizontally transposed from the representations used in this chapter, i.e. with N-3 to the north-west , mainly to draw attention to their structural similarity to the pyrimidine ring of the nucleic acid purines, which are traditionally drawn with the pyrimidine ring on the left. There are relatively few naturally occurring pyr-azines or pyridazines. 

EidinoffML, Knoll JE, Marano B, Cheong L. Pyrimidine Studies. I Effect of DON (6-diazo-5-oxo-L-norleucine) on incorporation of precursors into nucleic acid pyrimidines. Cancer Res. 18 105-109, 1958. 

Uracils are analogues of a very important building element of nucleic acids, pyrimidine, and thus might be incorporated in principle in nucleic acids. However, experiments of McGahen and Hoffmann (1963a,b) performed on desoxyribonucleic acids showed that bromacil is not incorporated in nucleic acids. 

The coloured parts of the molecules below emphasize the characteristic features of the bases, purine bases in nucleic acids pyrimidine bases in nucleic acids... 

Pyrimidine 1,3-diazine, a heterocyclic compound, consisting of a six-membered ring with 2 nitrogen atoms (Fig.l), M, 80.1, m.p. 20-22°C, b.p. 124°C. The P. ring system is present in many natural compounds, e. g. antibiotics (nucleoside antibiotics), pterins, purines and vitamins, it is especially important in the pyrimidine bases. Cytosine (see). Uracil (see) and Thymine (see), which are constituents of nucleic acids. Pyrimidine itself does not occur naturally. Pyrimidine analogs (see) can also be incorporated into nucleic acids. 

Finally, as mentioned above, with the advent of a technology for manipulation of nucleotides, the free uridine nucleotides were recognized as intermediates in the incorporation of orotate into the nucleic acid pyrimidines 2), and it became apparent that the first product of this pathway to possess a nucleic acid base was uridylate. 

With in vivo experiments, Hurlbert and Potter ) first showed that in rat liver, uridine nucleotides were intermediates in the conversion of orotate to nucleic acid pyrimidines the first of the three uridine phosphates to become labeled in this process was the monophosphate, uridylate (UMP) IS). The synthesis of uridylate from orotate takes place in two steps (a) the condensation of orotate with PP-ribose-P to form orotidylate (orotidine 5 -monophosphate, or OMP), and (b) decarboxylation of orotidylate. 

As early as 1949, it was demonstrated that injected or " C-labeled orotic acid was readily incorporated into DNA and RNA of mammalian tissue, indicating that orotic acid is a precursor of nucleic acid pyrimidine. The next step in pyrimidine biosynthesis is the formation of the first nucleotide in the sequence. It involves the reaction between ribosyl pyrophosphate and orotic acid to yield 5 -orotidylic acid the reaction is catalyzed by orotidylic pyrophosphorylase. Thus, the first steps of pyrimidine biosynthesis differ from the early steps of purine biosynthesis in at least two ways. Orotic acid, instead of being synthesized atom by atom as is the case for the purine ring, is made from the condensation of rather large molecules, namely, carbamyl phosphate and aspartic acid. Furthermore, all the steps of purine biosynthesis occur at the level of the nucleotide, but the the pyrimidine ring is closed at the level of the base. 

The initial evidence that nucleic acid pyrimidines could be synthesized from small molecules came from the work of Barnes and Schoenheimer. 1 Griffiths, M., /. Biol. Chem. 197, 399 (1962). 

Since Hammarsten s results showed that not only the pyrimidines of PNA but also those of DNA were labeled after administration of labeled cytidine, it was concluded that this was indirect evidence for the conversion of a pyrimidine riboside to a pyrimidine desoxyriboside. The reason for this was that cytidine could not have been split to cytosine and then reincorporated into desoxycytidine, since it had been shown earlier that the free base, cytosine, could not be utilized for the synthesis of nucleic acid pyrimidines. The possibility should not be overlooked, however, that the above conversion may possibly occur at the nucleotide level thus, cytidylic acid, in which the phosphate is attached to the nucleoside, may be the intermediate in the transformation of PNA to DNA pyrimidines. 

Since the orotic acid required by Lactobacillus could be replaced partially by carbamylaspartic acid, the latter compound was investigated further as a possible pyrimidine precursor labeled carbamylaspartic acid was as effective as orotic acid in labeling the nucleic acid pyrimidines of this microorganism (339). If ureidosuccinic acid were formed from oxalacetate or aspartate, it would be possible to outline the formation of the pyrimi-... 

Occurs in milk and other biol. systems. Key compd. involved in biosynth. of nucleic acid pyrimidine bases. Shows bacteriostatic and cytostatic props. Forms metal complexes. Uricosuric agent. Used in photometric detn. of Zn. Cryst. (H2O). Mp 322-325°, Mp 345-346°. 

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