Add time:08/28/2019         Source:sciencedirect.com

Publisher SummaryThis chapter discusses the biosynthesis of purines and pyrimidines. The vitamin, folic acid, is converted to its coenzyme form, tetrahydrofolic acid, by a pyridine nucleotide-dependent enzyme, dihydrofolate reductase. In turn, tetrahydrofolate serves as the carrier of various one-carbon groups that are added to, or abstracted from, metabolites such as histidine, serine, methionine, purines, and thymidylate. Tetrahydrofolate, thus, plays an important role in the synthesis of purines and pyrimidines, although its action is different in each instance. Two separate steps in the biosynthesis of purines involve the addition of a formyl group to effect ring closure. Conversely, pyrimidines are synthesized by a sequence that does not involve one-carbon units or folate coenzymes. However, important conversions external to the pyrimidine ring, hydroxymethylation or methylation at C-5, require tetrahydrofolate. Dihydrofolate reductase appears to have two functions in the cell: (1) the synthesis of tetrahydrofolate from the vitamin and (2) participation in the thymidylate synthesis cycle. A very interesting property of dihydrofolate reductases is their extreme sensitivity to folate antagonists containing a 4-amino group.

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