Pyrimidine catabolism reductive pathway

Uracil was degraded similarly via dihydrouracil and 8-ureidopropionic acid to 9-alanine (Fig. 26). These findings have also been demonstrated under a variety of experimental conditions, using isotopes in vivo and in vitro (415-419) and in studies with isolated enzyme systems (430, 431)-In support of the importance of reduced pyrimidines, dihydrouracil has been foimd in beef spleen (433). A similar reductive pathway for uracil catabolism was found in bacteria (43S 43B) and in Neurospora crasaa (436). 

In a study of the catabolic pathway of pyrimidines, it was found that the reduction of uracil was blocked almost completely by 5-cyanouracil (XXXV) in an in vitro test with the rat enzyme dihydropyrimidine dehydrogenase [303]. 5-Halogenated uracils and thymine are weakly active in this regard, and 5-acetyluracil and 5-trifluoromethyluracil are completely inert. 

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). 

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. 

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