Chapter 36 



Biosynthesis of Pyrimidine Nucleotides 



George W. Crosbie 

 Department of Biochemistry, The University of Glasgow, Glasgow, Scotland 



I. Introduction 323 



II. Biosynthesis of .Uridine Nucleotides 323 



1. Biosynthesis of Uridine-5'-phosphate 323 



2. Biosynthesis of Uridine-5'-di- and triphosphates 331 



III. Biosynthesis of Cytidine and Deoxycytidine Nucleotides 332 



1. Biosynthesis of Cytidine-5'-mono-, di-, and triphosphates 332 



2. Biosynthesis of Deoxycytidine-5'-mono-, di-, and triphosphates 335 



3. Biosynthesis of 5-Hydroxymethyldeoxycytidine-5'-phosphate 336 



IV. Biosynthesis of Thymidine Nucleotides 337 



1 . Biosynthesis of Thymidine-5'-phosphates 337 



V. Alternative Pathways of Pyrimidine Nucleotide Synthesis 347 



I. Introduction 



Information regarding the mechanism of pyrimidine nucleotide biosyn- 

 thesis has been considerably consolidated since the reviews of Reichard 1 

 and Schlenk 2 were written. The emphasis of the experimental approaches 

 to the investigation of the synthetic mechanisms has shifted from isotope 

 incorporation studies to the study of the relevant enzymes in cell-free sys- 

 tems. It is the purpose of this chapter to review briefly the mechanisms in- 

 volved in pyrimidine nucleotide biosynthesis with particular reference to 

 recent investigations of thymidylic acid synthesis. 



II. Biosynthesis of Uridine Nucleotides 



1. Biosynthesis of Uridine-5'-phosphate 



a. Biosynthesis from Small Molecules 



Early investigations of pyrimidine nucleotide biosynthesis involved either 

 a study of the incorporation of labeled small molecule precursors into the 

 polynucleotide pyrimidines of microorganisms, whole animals, tissue slices, 



1 P. Reichard, in "The Nucleic Acids" (E. Chargaff and J. N. Davidson, eds.), 

 Vol. II, p. 277. Academic Press, New York, 1955. 



2 F. Schlenk, in "The Nucleic Acids" (E. Chargaff and J. N. Davidson, eds.), Vol. 

 II, p. 309. Academic Press, New York, 1955. 



323 



