Pyrimidines catabolism

The ring system of pyrimidines is assembled before it is attached to ribose phosphate. 

During breakdown, the nucleoside is formed first, then the base. Ringopening reactions of the base complete the degradation. 

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The biosynthesis of purines and pyrimidines is stringently regulated and coordinated by feedback mechanisms that ensure their production in quantities and at times appropriate to varying physiologic demand. Genetic diseases of purine metabolism include gout, Lesch-Nyhan syndrome, adenosine deaminase deficiency, and purine nucleoside phosphorylase deficiency. By contrast, apart from the orotic acidurias, there are few clinically significant disorders of pyrimidine catabolism. 

Unlike the end products of purine catabolism, those of pyrimidine catabolism are highly water-soluble COj, NH3, P-alanine, and P-aminoisobutyrate (Figure 34-9). Excretion of P-aminoisobutyrate increases in leukemia and severe x-ray radiation exposure due to increased destruction of DNA. However, many persons of Chinese or Japanese ancestry routinely excrete P-aminoisobutyrate. Humans probably transaminate P-aminoisobutyrate to methylmalonate semialdehyde, which then forms succinyl-CoA (Figure 19-2). 

Since the end products of pyrimidine catabolism are highly water-soluble, pyrimidine overproduction results in few clinical signs or symptoms. In hypemricemia associated with severe overproduction of PRPP, there is overproduction of pyrimidine nucleotides and increased excretion of p-alanine. Since A, A -methyl-ene-tetrahydrofolate is required for thymidylate synthesis, disorders of folate and vitamin Bjj metabofism result in deficiencies of TMP. 

Gross E, Seek K, Neubauer S et al. High-throughput genotyping by DHPLC of the dihydropyrimidine dehydrogenase gene implicated in (fluoro)pyrimidine catabolism. Int J Oncol 2003 22 325-332. 

Sparidans RW, Bosch TM, Jorger M et al. Liquid chromatography-tandem mass spectrometric assay for the analysis of uracif 5,6-dihydrouracil and beta-ureidopropionic acid in urine for the mesurement of the aetivities of the pyrimidine catabolic etaymes. J Chromatogr B Analyt Technol BiomedLife Sci 2006 839 45-53. 

Cytosol Glycolysis, glycogenesis and glycogenolysis, hexose monophosphate pathway, fatty acid synthesis, purine and pyrimidine catabolism, aminoacyl-tRNA synthetases... 

Pathways for pyrimidine catabolism. The major end product from cytosine and uracil is y6-alanine, from thymine it is jS-aminoisobutyrate. 

Pyrimidine catabolism occurs mainly in the liver. In contrast to purine catabolism, pyrimidine catabolism yields highly soluble end products. Pyrimidine nucleotides are converted to nucleosides by 5 -nucleotidase. 

Purine Catabolism Pyrimidine Catabolism HEME BIOTRANSFORMATION... 

Synthesis of these substances is carefully controlled, because it is metabolically expensive in terms of both energy and precursor molecules. Many, but not all, purines and pyrimidines can be interconverted. The catabolism of purines and hemes produces unique products, whereas pyrimidine catabolism produces common products. The catabolism of purines produces uric acid, which in excess can produce gout. The catabolism of hemes produces bile pigments which, when in excess in the circulation, are referred to as jaundice, and when excreted normally, add pigmentation to the feces. 

Pyrimidine catabolism. The steps in the catabolism of cytosine and uracil are shown with corresponding structures the steps for thymine are shown only in... 

See also Pathways in Nucleotide Metabolism, Nucleotide Salvage Synthesis, Purine Degradation, Pyrimidine Catabolism... 

See also Figure 22.11, Coenzyme A, Amino Acids Not In Proteins, Pyrimidine Catabolism... 

Pathways for pyrimidine catabolism are shown in Figure 22.11. Pyrimidine bases are broken down through a common uracil intermediate, which is subsequently converted to dihydrouracil, followed by / -ureidopropionic acid, and finally / -alanine, ammonia and C02. ... 

Hydropyrimidine hydratase catalyzes the following reaction in pyrimidine catabolism Dihydrouracil + H20 <=> / -Ureidopropionic Acid... 

Ureidopropionase is an enzyme in pyrimidine catabolism that catalyzes the reaction that follows / -Ureidopropionic acid + H2O <=> Alanine + NH4+ + CO2... 

Salvage Synthesis and Pyrimidine Catabolism (Figure 22.11) Deoxyribonucleotide Biosynthesis and Metabolism (Figure 22.12)... 

Other compounds serving essential biological functions are the products of purine and pyrimidine catabolism. Since these compounds are metabolic wastes, their production should be relatively large. The relatively high concentration of urea in seawater perhaps reflects this (McCjirthy, 1970 Remsen et al., 1974). The release of relatively high amounts of glycolic acid (bio-... 

Recall Compare the fates of the products of purine and pyrimidine catabolism. 

Purines break down to various products, depending on the species. These products are then excreted, representing a m or means of nitrogen excretion for many organisms. Pyrimidine catabolism yields, in addition to NH and COg, the salvageable product p-alanine, which is a breakdown product of both cytosine and uracU. 

Kim, S. West, T.P., Pyrimidine catabolism in Pseudomonas aeruginosa. FEMS Microbiol. Lett., 77 (1991) 175-180. 

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