Pyrimidines and Purines

Glutamine as an important source for the synthesis of purines, pyrimidines and amino sugars is essential for most cell lines, too. High concentrations of glutamine may also effect cell growth indirectly as the major end-products are lactate and ammonia [15]. Both known to be toxic metabohtes. 

Under physiologic conditions, the amino and oxo tautomers of purines, pyrimidines, and their derivatives predominate. 

Purines, pyrimidines and their nucleosides and nucleoside triphosphates are synthesized... 

Treatment of bacterial cells with appropriate concentrations of such substances as eetrimide, chlorhexidine, phenol and hexylresorcinol, causes a leakage of a group of eharacteristic chemical species. The potassium ion, being a small entity, is the fust substance to appear when the cytoplasmic membrane is damaged. Amino acids, purines, pyrimidines and pentoses are examples of other substances which will leak horn treated cells. 

Voelter W, Records R, Bunnenberg E, Djerassi C (1968) Magnetic circular dichroism studies, vi. investigation of some purines, pyrimidines, and nucleosides. J Am Chem Soc 90 6163—6170... 

Antimetabolites. This class of drugs includes purine, pyrimidine, and folic acid analogs that have been successfully used to treat various carcinomas, autoimmune diseases, and dermatological disorders such as psoriasis. Because of their structural similarities to normal components of DNA and RNA synthesis, they are capable of competing with the normal macromolecules and alkylating biological nucleophiles. 

Purines, pyrimidines, and the corresponding nucleosides have been separated in reversed phase systems. The five mqior nucleosides as well as inosine and xanthosine and the corresponding seven bases were separated by Hartwick and Brown (405). The selective determination of adenosine in the presence of other serum components has been reported (406). 

None of the extracts from unchlorinated model compounds were significantly different from the negative controls. Extracts of chlorinated purines-pyrimidines and chlorinated nucleosides-nucleotides were also found to be not significantly mutagenic. However, the extracts of all three chlorinated humic acids and the chlorinated amino acids were... 

In contrast to our understanding of the pathways by which the purines, pyrimidines and histidine are formed, we know much less about the formation of other equally important... 

Bergmeyer. fi ll. Metabolites 2 iRI and Dicarhoxstic Acids. Purines. Pyrimidines and Oerirutnes. Coenzvmes and inorganic Compounds. Vot. 2, John Wiley Sons, Inc. New York. NY. 1985. 

Precursors in the biosynthesis of riboflavin include purines, pyrimidines, and ribose. Intermediate in the synthesis is 6,7-diinethyl-8-ribityllumazine. In plants, riboflavin production sites are found in leaves, germinating seeds, and root nodules. Storage sites in animals are heart and liver, with small amounts in Ihe kidneys. Riboflavin in overdose is essentially nontoxic to humans. 

The above review shows the progress that has been made in the last 30 years. The prebiotic synthesis of amino acids, purines, pyrimidines, and sugars is understood at a basic level, although more details of the reactions are needed. The polymerization processes are less well understood, and while some of them are plausible it is necessary to work them out in greater detail. The template polymerization reactions are an exciting beginning and may show how genetic information started to accumulate. So far the problem of nucleic acid directed enzyme synthesis has not been dealt with on an experimental level. The problems in this area, which are very difficult, are considered by other speakers in this symposium. 

The reaction of many compounds of biological interest with ammonium bicarbonate on thin-layer plates permits detection of 10-100-ng amounts of these compounds [141]. Many compounds in the lipid, steroid, sugar, amino acid, purine, pyrimidine and alkaloid classes can be analyzed in this way (Table 4.26). 

In acute and chronic urinary tract infection, the combination of trimethoprim and sulfamethoxazole (Bactrim, Septra) exerts a truly synergistic effect on bacteria. The sulfonamide inhibits the utilization of p-amino-benzoic acid in the synthesis of folic acid (Figure 2.3), whereas trimethoprim, by inhibiting dihydrofolic acid reductase, blocks the conversion of dihydrofolic acid to tetrahydrofolic acid, which is essential to bacteria in the denovo synthesis of purines, pyrimidines, and certain amino acids. Because mammalian organisms do not synthesize folic acid and therefore need it as a vitamin in their daily diets, trimethoprim-sulfamethoxazole does not interfere with the metabolism of mammalian cells. 

The active form of folate is the tetrahydro-derivative that is formed through reduction by dihydrofolate reductase. This enzymatic reaction (Figure 29.5) is inhibited by trimethoprim, leading to a decrease in the folate coenzymes for purine, pyrimidine, and amino acid synthesis. Bacterial reductase has a much stronger affinity for trimethoprim than does the mammalian enzyme, which accounts for the drug s selective toxicity. [Note Examples of other folate reductase inhibitors include pyrimethamine, which is used with sulfonamides in parasitic infections (see p. 353), and methotrexate, which is used in cancer chemotherapy (see p. 378).]... 

Vitamin B12 is required by only two enzymes in human metabolism methionine synthetase and L-methylmalonyl-CoA mutase. Methionine synthetase has an absolute requirement for methylcobalamin and catalyzes the conversion of homocysteine to methionine (Fig. 28-5). 5-Methyltetrahydrofolate is converted to tetrahydrofolate (THF) in this reaction. This vitamin B12-catalyzed reaction is the only means by which THF can be regenerated from 5-methyltetrahydrofolate in humans. Therefore, in vitamin B12 deficiency, folic acid can become trapped in the 5-methyltetrahydrofolate form, and THF is then unavailable for conversion to other coenzyme forms required for purine, pyrimidine, and amino acid synthesis (Fig. 28-6). All folate-dependent reactions are impaired in vitamin B12 deficiency, resulting in indistinguishable hematological abnormalities in both folate and vitamin B12 deficiencies. 

As a class, the compounds derived from purine and pyrimidine bases are of considerable biochemical interest, particularly if they are the constituents of the nucleic adds. With their many hydrogen-bonding donor and acceptor functions, these molecules can interact specifically with the enzymes involved in the metabolism of the nucleic acids and with regulatory proteins. Purines, pyrimidines, and their derivatives have been used most successfully in the investigations of biological processes and have found application in pharmacology [520, 521]. The same is true for the barbiturates, where the main emphasis is in pharmaceutical industry. 

In a monumental piece of research, Roques and co-workers 235-239) have employed exceedingly sophisticated and difficult high-field H- and P-NMR experiments to examine the interaction of nonlinear bispyridocarbazoles, such as ditercalinium (212), with small polynucleotides. As in their earlier work on monomers 233), the self-complementary tetra- and hexanucleotides were used. It was found that ditercalinium is a bis-intercalator with a preference for alternating sequences, pyrimidine-purine or purine-pyrimidine, and, in agreement with the classic pyrimidine-purine model 240,241), it was found that the linking chain lies in the major groove of the helix. 

Biologically active lluorinated purines, pyrimidines, and pteridines, advances in preparation of 87T3123. 

Ferris JP, Joshi PC, Edelson EH, Lawless JG. HCN a plausible source of purines, pyrimidines and amino acids on the primitive earth. J. Mol. Evol. 1978 11 293-311. 

Purines, pyrimidines and their nucleosides and nucleoside triphosphates are synthesized in the cytoplasm. At this stage the antifolate drugs (sulphonamides and dihydrofolate reductase inhibitors) act by interfering with the synthesis and recycling of the co-factor dihydrofolic acid (DHF). Thymidylic acid (2-deoxy-thymidine monophosphate, dTMP) is an essential nucleotide precursor of DNA synthesis. It is produced by the enzyme thymidylate synthetase by transfer of a methyl group from tetrahydrofolic acid (THF) to the uracil base on uridylic acid (2-deoxyuridine monophosphate, dUMP) (Fig. 12.5). THF is converted to DHF in this process and must be reverted to THF by the enzyme dihydrofolate reductase (DHFR) before... 

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