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Human Tissue Information Processing Proceedings of the 2nd WSEAS International Conference on BIOMEDICAL ELECTRONICS and BIOMEDICAL INFORMATICS Human tissue information processing JELENKA SAVKOVIC-STEVANOVIC Faulty of Technology and Metallury, Belgrade University,Karnegijeva 4, 11000 Belgrade SERBIA, [email protected] Abstract:-In this paper the metabolisms of the purines and pyrimidines and their nucleosides and nucleotides have examined. The biomedical important is de novo synthesis which is permiting purine and pyrimidine analogs with potential as anticancer drugs to be incorporated into DNA. The synthesis rates of purine and pyrimidine oxyribonucleotides and deoxyribonucleotides are subject to precise regulation. The obtained results of investigation in this paper have shown human tissue information processing incorporating nucleic acids. Keywords: Purine bases, pyrimidine bases, physicochemical properties, DNA,RNA, tissue. chemotherapy as enzyme inhibitors and can replace 1 Introduction the naturally occurring nucleotides in nucleic acids. The nucleotides participate in a wide variety of Therapeutic attempts to inhibit the growth of biochemical processes. Perhaps the best known role cancer cells or certain viruses have often employed of purine and pyrmidine nucleotides is to serve as administration of analogs of bases, nucleosides, or the monomeric precursors of RNA and DNA[1-4]. nucleotides that inhibit the synthesis of either DNA However, the purine ribonucleotides serve also as or RNA.Such compounds include 5-fluorouracil, the ubiquitous high energy source, ATP, as 5’-iodo-2’-deoxyuridine, 6-thioguanine,6- regulatory signals (cycle AMP [cAMP] and GMP mercaptopurine, 6- azauridine, and arabinosyl [cGMP]), and as components of the coenzymes cytosine. as azauridine. Allopurinol, a purine and of the methyl group donor S adenosil analog, is widely used in the treatment of gout. methionine. The pyrimidine nucleotides in Neither nucleotides nor their parent purine and addition to providing monomeric precursors for pyrimidine bases in the diet are incorporated into nucleic acid synthesis, also serve as high energy human tissue nucleic acids or into purine or intermediates, such as UDP - glucose and UDP- pyrimidine coenzymes such as ATP or NAD. Even galactose in carbohydrate metabolism and CDP- when a diet rich in nucleoproteins is ingested, acylglycerol in lipid synthesis. human subjects form the constituents of tissue The heterocyclic bases purine and pyrimidine nucleic acids from amphibolic intermediates. This are the parent molecules of nucleosides and de novo synthesis permits purine and pyrimidine nucleotides. Nucleotides are ubiquitous in living analogs with potential as anticancer drugs to be cells, where they perform numerous key functions. incorporated into DNA. The rates of synthesis of Examples include incorporation, as their ribose purine and pyrimidine oxy- and (RNA) or deoxyribose (DNA) monophosfates, into deoxyribonucleotides are subject to precise nucleic acids, energy transduction (ATP) , parts of regulation. Mechanisms have evolved to ensure coenzymes (AMP) acceptors for oxidative production of these compounds in quantities and at phosphorylation (ADP) allosteric regulators of times appropriate to meet varying physiologic enzyme activity, and second messengers (cAMP), demand. In addition to de novo synthesis, these cGMP). include “salvage” pathways for reutilization of purine or pyrimidine bases released by degradation The structure and function of the purines and of nucleic acids in vivo. Human diseases that pyrimidines and their nucleosides and nucleotides involve abnormalities in purine or pyrimidine were studied in numerous literature. metabolism include gout, Lesch-Nyhan syndrome, In this paper the metabolism of the purines and Reye’s syndrome, adenosine deaminase deficiency, pyrimidines and their nucleosides and nucleotides and purine nucleoside phosphorylase deficiency. have examined. 3 Structure and properties of purine and pyrimidine base 2 Biomedical important Purine and pyrimidine bases that occur in the Synthetic analogs of naturally occurring nucleotides are derived by substitution on the ring nucleotides find application in cancer ISSN: 1790-5125 64 ISBN: 978-960-474-110-6 Proceedings of the 2nd WSEAS International Conference on BIOMEDICAL ELECTRONICS and BIOMEDICAL INFORMATICS structures of the parent substances, purine and attached at N9 . Guanosine consists of guanine pyrimidine. with with D-ribose attached at N9 . ytidine is cytosine with ribose attached at its N position. The three major pyrimidine bases present in 1 Uridine consists of ribose attached at the position the nucleotides of both procaryotes and eukaryotes of uracil. are cytosine, thymine, and uracil. The purine bases adenine and guanine are the two major purines The 2’-deoxyribonucleosides consist of 2- found in living organisms. Two other purine bases, deoxyribose attached to purine or pyrimidine bases. hypoxanthine and xanthine, occur as intermediates Attachment of the ribose or 2-deoxyribose to the in the metabolism of adenine and guanine. In ring structuresis through an glycosidic bond, which humans, a completely oxidizes purine base, uric is relatively acid labile. Although, theoretically, acid, is formed as the end product catabolism. free rotation of the sugar moiety and the purine or pyrimidine In natural materials, unusual bases occur in he addition to the 5 major described bases. Some of Ring structure occurs about this N-glycosidic these unusual substituted bases are present only in bond, steric hindrance in fact hinders free rotation. the nucleic acids of bacteria and viruses, but many In the naturally occurring nucleosides, the anti are also found in the DNA and transfer RNAs of conformation is strongly favored over the syn both prokaryotes and eukaryotes. For example, form. The anti form is necessary for the proper both bacterial and human DNA contain significant positioning of the complementary purine and quantities of 5-methylcytosine, bacteriophages pyrimidine bases in the double stranded B-form of contain 5- hydroxyl-methyl-cytosine. Unusual deoxyribonucleic acid. bases presenting the messenger RNA molecules of Nucleotides are nucleosides phophotylated on mammalian cells include N6, N6-dimethyladenine, one or more of the hydroxyl groups of the sugar and N7-methylguanine. An uracil modified at theN 3 (ribose or deoxyribose). Thus, adenosine position by the attachment of an (α-amino, α- monophosphate(AMP or adenylate) is adenine + carboxyl)-propyl group has also been detected in ribose +phosphate. 2’-Deoxyadenosine mono- bacteria. phosphate (dAMP or deoxyadenylate) consists of In plants, a series of purine bases ontaining 2-deoxyribose + phosphate. The only sugar methyl substituents occurs. Many hve commonly found attached to uracil is ribose, and pharmacologic properties. Examples are coffee, that commonly found attached to thymine is 2- which contains caffeine (1,3,7 –trimethylxanthine), deoxyribose. Therefore, thymidic acid (TMP) is tea, which contains theophylline (1,3- thymine +2-deoxyribose +phosphate, and uridylic dimethylxanthine). acid (UMP) is uracil +phosphate. DNA is a polymer of thymidilic acid, 2’-deoxycytidilic acid, Because of keto-enol tautomerism, thses 2’-deoxyadenylic acid, and 2’-deoxyguanylic acid. aromatic molecules can exist in a lactim or lactam RNA is a polymer containing uridylate, citydilate, form, the latter is by far the predominant tautomer adenylate, and guanylate. of guanine or thymine under physiologic conditions. There areexpectations to the above structures of nucleotides. For example, in tRNA riboeis At neutral pH, guanine is the least soluble of occasionally attached to uracil at the 5 position, the bases, followed in thi respect y xanthyne. establishing a carbon-to-carbon linkage instead of Although uric acid as urate is relatively soluble at the usual nitrogen –to-carbon linkage. This a neutral pH, it is highly insoluble in solutions unusually compound is called pseudo uridine (ψ). with a lower pH, such as urine. Guanine is not a tRNA molecules contain another unusual normal constituent of human urine, but xanthyne nucleotide structure, i.e. thymine attached to ribose and uric acid do occur in human urine. These latter monophosphate. Pseudurydilic acid (ψMP) is 2 purines frequently occur as constituents of similarly rearranged from urydilic acid after the t urinary tract stones. RNA molecule has been synthesized. The abbervations A,G,C,T, and U may be used to designate the nucleosides that contain adenine, 4 Nucleosides and nucleotides guanine, cytosine thymine, or uracil, respectively. The free bases are much less abundant in nature For example, guanosine containing 2’-deoxyribose than are their nucleosides and nucleotides. The would be designated dG (deoxyguanosine) and the nucleoside is composed of a purine or a pyramidine corresponding monophosphate with the pphosphate base to which a sugar (usually either D-ribose or esterified to the carbon 3 of the deoxyribose moiety 2-deoxyribose) is attached in β –linkage at N9 or designated dG-3’-MP. Generally, when the N1, respectively. Thus, the adenine ribonucleside phosphate is esterified to the carbon 5 of the ribose adenosine consists of adenine with D-ribose or deoxyribose moiety, the prefixed primed (5’) is omitted. For example, gunosine 5’- monophosphate ISSN: 1790-5125 65 ISBN: 978-960-474-110-6 Proceedings of the 2nd WSEAS International Conference on BIOMEDICAL ELECTRONICS and BIOMEDICAL INFORMATICS would be abbreviated GMP , while the 5’- conversion
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