Pyrimidine catabolism oxidative pathway

The catabolism of pyrimidine nucleotides, like that of purine nucleotides (Chapter 10), involves dephosphorylation, deamination, and glycosidic bond cleavage. In contrast to purine catabolism, however, the pyrimidine bases are most commonly subjected to reduction rather than to oxidation. An oxidative pathway is found in some bacteria however. 

Whether the pathways of oxidation of pyrimidines by bacteria are valid for mammalian systems remains to be determined. The formation of isobarbituric acid, as suggested by Cerecedo, is not in accord with the bacterial studies discussed above. The appearance of urea, however, as a final product of pyrimidine catabolism, agrees with the early observations of Plentl and Schoenheimer and of Bendich et alM Their experiments showed that N Mabeled pyrimidines were converted to labeled urea by the rat. 

We should note at this point that the TCA cycle is more than just a means of producing NADH for oxidative phosphorylation. The pathway also provides a number of useful intermediates for other, often synthetic, pathways. For example, citrate is the starting substance for fat synthesis (Chapter 9) succinyl-CoA is required for haem production and 2-oxoglutarate and oxaloacetate in particular are involved with amino acid and pyrimidine metabolism. Pathways which have dual catabolic/anabolic functions are referred to as amphibolic . 

Pyrimidine ribonucleotides, like those of purines, may be synthesized de novo from amino acids and other small molecules (Chapter 11). Preformed pyrimidine bases and their ribonucleoside derivatives, derived from the diet of animals or found in the environment of cells, may be converted to ribonucleotides via nucleoside phosphorylases and nucleoside kinases. In some cells a more direct pyrimidine phosphoribosyltransferase pathway has also been recognized (Chapter 12). Ribonucleotides are catabolized by dephosphorylation, deamination, and cleavage of the glycosidic bond, to uracil. Uracil may be either oxidatively or reductively cleaved, depending on the organism involved, and can be converted to CO and NH (Chapter 13). 

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