Purine and Pyrimidine Nucleotides

Proteias are metabolized coatiauously by all living organisms, and are ia dyaamic equilibrium ia living cells (6,12). The role of amino acids ia proteia biosyathesis has beea described (2). Most of the amino acids absorbed through the digestioa of proteias are used to replace body proteias. The remaining portioa is metabolized iato various bioactive substances such as hormones and purine and pyrimidine nucleotides, (the precursors of DNA and RNA) or is consumed as an energy source (6,13). 

Purine and pyrimidine biosynthesis parallel one another mole for mole, suggesting coordinated control of their biosynthesis. Several sites of cross-regulation characterize purine and pyrimidine nucleotide biosynthesis. The PRPP synthase reaction (reaction 1, Figure 34-2), which forms a precursor essential for both processes, is feedback-inhibited by both purine and pyrimidine nucleotides. 

Goordinated regulation of purine and pyrimidine nucleotide biosynthesis ensures their presence in proportions appropriate for nucleic acid biosynthesis and other metabolic needs. 

Information within the single strand of RNA is contained in its sequence ( primary strucmre ) of purine and pyrimidine nucleotides within the polymer. The sequence is complementary to the template strand of the gene from which it was transcribed. Because of this... 

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. 

Another important vitamin is folate, which is required for purine and pyrimidine nucleotide synthesis. Since folate and its derivatives are generally lipo-phobic anions, they do not traverse biological membranes via simple diffusion but rather have to be taken up into the cells by specific transport processes... 

Volume LI. Purine and Pyrimidine Nucleotide Metabolism Edited by Patricia A. Hoffee and Mary Ellen Jones... 

Glutamine Purine and pyrimidine nucleotides, amino sugars... 

Tumour cells also require glutamine as a fuel for energy generation and as a precursor for the synthesis of purine and pyrimidine nucleotides for DNA and RNA synthesis. The roles and importance of glutamine in tumour cells and possible competition between the cells for glutamine are discussed in Chapter 21. The pathway for the metabolism of glutamine is similar to that in the immune cells. 

DNA and RNA synthesis De novo formation of purine and pyrimidine nucleotide Nucleoside diphosphate reductase Thymidylate synthase Polymerase reactions Chapter 20... 

Figure 17.38 A simple diagram illustrating the two roles of glutamine (i) generation of ATP, via glutaminolysis, (ii) formation of purine and pyrimidine nucleotides, for the synthesis of nucleic acids in proliferating cells (Chapter 20). ( represents the carbon atoms of glutamine, one of which is released as CO2 and the others are converted to aspartate, via part of the Krebs cycle (Chapter 9). (N) represents the amide nitrogen of glutamine.

Figure 20.8 Summary of pathways for de novo synthesis of purine and pyrimidine nucleotides. C represents transfer of a single carbon atom (a one-carbon transfer). Details are provided in Appendix 20.1. IMP - inosine monophosphate. For thymi-dylate synthesis, see Figure 20.12a.

Antimetabolites (inhibition of purine and pyrimidine nucleotide synthesis) Methotrexate Folic acid antagonist, inhibits tetrahydrofolate reductase and therefore dTMP synthesis 6-Mercaptopurine Interferes with purine synthesis 5-Fluorouracil Inhibits dTMP synthesis ... 

Pemetrexed is chemically similar to folic acid. It inhibits three enzymes used in purine and pyrimidine synthesis - thymidylate synthetase, dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase. By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA. In 2004 it was approved for treatment of malignant pleural mesothelioma and as a second-line agent for the treatment of non-small cell lung cancer. Adverse effects include gastrointestinal complaints, bone marrow suppression, alopecia, allergic and neurotoxic reactions. 

Yields of Destruction of Base Components of Various Purine and Pyrimidine Nucleotides on Irradiation of Their Aqueous Solutions (2 x 10 iM, pH = 7.0) with X-Rays (200 kV) in the Presence of Oxygen... 

Purine and pyrimidine nucleotides are essential for a vast number of biological processes such as the synthesis of RNA, DNA, phospholipids, glycogen, and the si-alylation and glycosylation of proteins. Both purines and pyrimidines can be synthesized de novo in mammalian cells through multistep processes. In addition to the de novo synthesis, purine nucleotides can also be synthesized via the salvage of... 

We examine here the biosynthetic pathways of purine and pyrimidine nucleotides and their regulation, the formation of the deoxynucleotides, and the degradation of purines and pyrimidines to uric acid and urea. We end with a discussion of chemotherapeutic agents that affect nucleotide synthesis. 

All organisms synthesize, interconvert, and catabolize various purine and pyrimidine nucleotides. However, cells of different types, or even the same cells in different stages of development, differ greatly in their ability to carry out some of the reactions involved, with some cells favoring one set of reactions and others another. In the rest of the chapter we deal with the details of these reactions. 

Andersson, M., L. Lewan, and U. Stenram. Compartmentation of purine and pyrimidine nucleotides in animal cells. Int. 

Purine and pyrimidine nucleotides are essential components of many biochemical molecules, from DNA and RNA to ATP and NAD. In recent years, the pyrimidine and especially the purine metabolism of parasitic helminths have been investigated extensively, mainly because they are different from the pathways in the mammalian host such that they have potential as targets for chemotherapeutic attack. For a review of purine and pyrimidine pathways in parasitic helminths and protozoa, see Berens et al. (1995). Although parasitic helminths do not synthesize purines de novo, but obtain them from the host, they do possess elaborate purine salvage pathways for a more economical management of this resource. Pyrimidines, on the other hand, are synthesized de novo by all parasitic flat-worms studied so far and, as with mammalian... 

Cells are able to synthesize genetic material (DNA, RNA) from endogenous metabolites known as purine and pyrimidine nucleotides (Fig. 36-3). Certain anticancer drugs are structurally similar to these endogenous metabolites and compete with these compounds during DNA/RNA biosynthesis. These drugs are therefore called antimetabolites because they interfere with the normal metabolites during cellular biosynthesis.16,80... 

Purine and pyrimidine nucleotides fill a variety of metabolic roles. They are the energy currency of the cell. In some cases, they are signaling molecules, acting like hormones directly or as transducers of the information. They provide the monomers for genetic information in DNA and RNA. 

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