Pyrimidine and Purine Metabolism

Sumi S, Kidouchi K, Ohba S et al. Automated screening system for purine and pyrimidine metabolism disorders using high performance liquid chromatography. J Chromatogr B Biomed Sci Appl 1995 672 233-239. 

Screening for Disorders of Purine and Pyrimidine Metabolism Using HPLC-Electrospray Tandem Mass Spectrometry... 

Ito T, van Kuilenburg ABP, Bootsma AH, Haasnoot AJ, van Cruchten AG, Wada Y, van Gen-nip AH (2000) Rapid screening of high-risk patients for disorders of purine and pyrimidine metabolism using HPLC-electrospray tandem mass spectrometry of liquid urine or urine-soaked filter paper strips. Clin Chem 46 445-452... 

This four-volume set has good chapters on disorders of amino acid, porphyrin, and heme metabolism. See also the chapters on inborn errors of purine and pyrimidine metabolism. 

Berens, R.L., Krug, E.C. and Marr, J.J. (1995) Purine and pyrimidine metabolism. In Marr, J. and Muller, M. (eds) Biochemistry and Molecular Biology of Parasites. Academic Press, New York, pp. 89-117. 

Berg, G. M., andj0rgensen, N. O. G. (2006). Purine and pyrimidine metabolism by estuarine bacteria. Aquat. Micro. Ecol. 42, 215—226. 

Shaw, T. and Locamini, S. A. (1995) Hepatic purine and pyrimidine metabolism implications for antiviral chemotherapy of viral hepatitis. Liver 15, 169-184. 

BIS. de Bersaques, J., Purine and pyrimidine metabolism in human epidermis. J. Invest. Dermatol. 48, 169-173 (1967). 

A few other less studied biochemical approaches such as purine and pyrimidine metabolism protein biosynthesis and lipid metabohsm in helminths also provide targets for antiparasitic drug design [83]. Like protozoal parasites, some helminths such as S. mansoni (adult and larval forms) lack de novo purine biosynthesis and, therefore, depend entirely on the salvage mechanism for their purine requirements. Similarly amino acid metabolism and biosynthesis of proteins has also been not worked out in many parasites [83a]. Although the helminths meet their requirements of amino acids by absorbing freely from the host, they may also synthesize some amino acids. For example. Fasciola hepatica, schistosomes and other trematodes produce proline by a reaction sequence given in Chart 8. Similarly H. diminuta can... 

Hyde, J. E. (2007). Targeting purine and pyrimidine metabolism in human apicomplexan parasites. Curr. Drug Targets 8,31-47. 

Reyes, P., Rathod, P. K., Sanchez, D. J., Mrema, J. E., Rieckmann, K. H., and Heidrich, H. G. (1982). Enzymes of purine and pyrimidine metabolism from the human malaria parasite, Plasmodium falciparum. Mol. Biochem. Parasitol. 5,275-290. 

Sherman, I. W. (1998b). Purine and pyrimidine metabolism of asexual stages. In "Malaria. Parasite Biology, Pathogenesis and Protection" (Sherman, ed.), pp. 177-184. ASM Press, Washington, DC. 

Thus, a large number of substances have been tested as inhibitors for the steps in purine and pyrimidine metabolism (Cory, in Devlin, 1986, p. 674 0. Inclnded are both synthetic compounds and compounds isolated from plants, bacteria, fungi, etc. The substances may be further classed as glutamine antagonists, antifolates, and antimetabolites. Whereas the first-mentioned substances are toxic in the extrane, the latter two classifications have been of main concern although they are toxic enough in their own right. 

Purine deoxyribonucleotides are derived primarily from the respective ribonucleotide (Fig. 6.2). Intracellular concentrations of deoxyribonucleotides are very low compared to ribonucleotides usually about 1% that of ribonucleotides. Synthesis of deoxyribonucleotides is by enzymatic reduction of ribonucleotide-diphosphates by ribonucleotide reductase. One enzyme catalyzes the conversion of both purine and pyrimidine ribonucleotides and is subject to a complex control mechanism in which an excess of one deoxyribonucleotide compound inhibits the reduction of other ribonucleotides. Whereas the levels of the other enzymes involved with purine and pyrimidine metabolism remain relatively constant through the cell cycle, ribonucleotide reductase level changes with the cell cycle. The concentration of ribonucleotide reductase is very low in the cell except during S-phase when DNA is synthesized. While enzymatic pathways, such as kinases, exist for the salvage of pre-existing deoxyribosyl compounds, nearly all cells depend on the reduction of ribonucleotides for their deoxyribonucleotide... 

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