This PPT contains topic on Biosynthesis of Purine and Pyrimidine Nucleotides. Book referred: https://www.amazon.in/BIOCHEMISTRY-SATYANARAYANA-5TH-2017/dp/B073Y7XGH4

2. • Nucleotides consist of a
– Nitrogenous base
– Pentose
– Phosphate
 The pentose sugar is D-ribose in ribonucleotides The pentose sugar is D-ribose in ribonucleotides
of RNA
 In deoxyribonucleotides of DNA, the sugar is 2-
deoxy D-ribose.

3. Biosynthesis of Purine Ribonucleotides
• Compounds contributing to the purine ring of
the nucleotides
Amino group of aspartate: N1 of purine.Amino group of aspartate: N1 of purine.
Formate of N10- formyl THF: C2 and C8.
Amide group of glutamine: N3 and N9.
Glycine: C4, C5 and N7.
CO2: C6.

4. Sources of individual atoms in Purine ring.

5. • Purine bases are formed as ribonucleotides.
• The purines are built upon a pre-existing
ribose 5-phosphate.ribose 5-phosphate.
• Liver: major site for purine nucleotide
synthesis.

6. Steps for the synthesis of inosine
monophosphate
The reactions for the pathway for the synthesis
of inosine monophosphate are briefly
described in the Steps below.described in the Steps below.
• Inosine monophosphate (IMP or inosinic acid)
is the ‘parent’ purine nucleotide.

7. Step 1
• Ribose 5-phosphate + ATP  Phosphoribosyl
pyrophosphate (PRPP)
• Ribose 5-phosphate: Starting material for• Ribose 5-phosphate: Starting material for
purine nucleotide synthesis.
• Ribose 5-phosphate is produced in the HMP
shunt of carbohydrate metabolism.

8. Step 2
• Phosphoribosyl pyrophosphate (PRPP)  5-
phosphoribosylamine by “PRPP glutamyl
amidotransferase” in presence of Glutamine.amidotransferase” in presence of Glutamine.
– Glutamine transfers its amide nitrogen to PRPP

9. Step 3
• Phosphoribosylamine + Glycine + ATP 
Glycinamide ribosyl 5-phosphate or
Glycinamide ribotide (GAR)Glycinamide ribotide (GAR)

10. Step 4
• Glycinamide ribosyl 5-phosphate + N10-
Formyl tetrahydrofolate  Formylglycinamide
ribosyl 5-phosphate by “Formyltransferase”ribosyl 5-phosphate by “Formyltransferase”
– N10-Formyl tetrahydrofolate donates the formyl
group.

11. Step 5
• Formylglycinamide ribosyl 5-phosphate +
Glutamine  Formylglycinamidine ribosyl 5-
phosphate by “Synthetase”phosphate by “Synthetase”
– Glutamine transfers the second amido amino
group.

12. Step 6
• Formylglycinamidine ribosyl 5-phosphate +
ATP  5-aminoimidazole ribosyl 5-phosphate
by “Synthetase”by “Synthetase”

13. Step 7
• 5-aminoimidazole ribosyl 5-phosphate + CO2
 aminoimidazole carboxylate ribosyl 5-
phosphate by “Carboxylase”phosphate by “Carboxylase”

14. Step 8
• Aminoimidazole carboxylate ribosyl 5-
phosphate + Aspartate + ATP 
aminoimidazole 4-succinyl carboxamideaminoimidazole 4-succinyl carboxamide
ribosyl 5-phosphate by “Synthetase”.

15. Step 9
• Aminoimidazole 4-succinyl carboxamide
ribosyl 5-phosphate  Aminoimidazole 4-
carboxamide ribosyl 5-phosphate bycarboxamide ribosyl 5-phosphate by
“Adenosuccinate lyase”
– Adenosuccinate lyase cleaves off fumarate.

16. Step 10
• Aminoimidazole 4-carboxamide ribosyl 5-
phosphate + N10-Formyl tetrahydrofolate 
Formaminoimidazole 4-carboxamide ribosyl 5-
phosphate by “Formyltransferase”phosphate by “Formyltransferase”
– N10-Formyl THF donates a one-carbon moiety to
produce formaminoimidazole 4-carboxamide
ribosyl 5-phosphate.

17. Step 11
• Formaminoimidazole 4-carboxamide ribosyl 5-
phosphate  inosine monophosphate by
“Cyclohydrolase”“Cyclohydrolase”
– with an elimination of water molecule.

18. Pathway for the synthesis of inosine
monophosphate
‘Parent’ Purine Nucleotide (Inosine
monophosphate), is given in Pathway below.

19. Continued…

20. Continued…

22. Salvage pathway for purines
The purines can be directly converted to the
corresponding nucleotides, and this process is
known as ‘salvage pathway’.known as ‘salvage pathway’.

23. Salvage pathways of purine nucleotide synthesis

24. Biosynthesis of pyrimidine ribonucleotides
• Aspartate, glutamine (amide group) and CO2
contribute to atoms in the formation of
pyrimidine ring
• Pyrimidine ring is first synthesized and then
attached to ribose 5-phosphate.

25. Sources of individual atoms in
pyrimidine ring

26. Step 1
• Glutamine + CO2 + ATP  Carbamoyl
Phosphate by “Carbamoyl Phosphate
Synthetase II”Synthetase II”
– Glutamine transfers its amido nitrogen to CO2 to
produce carbamoyl phosphate.

27. Step 2
• Carbamoyl Phosphate + Aspartate 
Carbamoyl aspartate by “Aspartate
transcarbamoylase”transcarbamoylase”

28. Step 3
• Carbamoyl aspartate  Dihydroorotate by
“Dihydroorotase”
– Dihydroorotase catalyses the pyrimidine ring– Dihydroorotase catalyses the pyrimidine ring
closure with a loss of H2O

29. Step 4
• Dihydroorotate  Orotate by “Dihydroorotate
dehydrogenase”
– NAD+ dependent dehydrogenation.– NAD+ dependent dehydrogenation.

30. Step 5
• Orotate + PRPP  Orotidine monophosphate
(OMP) by “Orotate phosphoribosyltransferase”
– NAD+ dependent dehydrogenation.– NAD+ dependent dehydrogenation.

31. Step 6
• Orotidine monophosphate  uridine mono-
phosphate (UMP) by “OMP decarboxylase”

32. Step 7
• Uridine mono-phosphate + ATP  UDP by
“kinase”
– UDP which serves as a precursor for the synthesis– UDP which serves as a precursor for the synthesis
of dUMP, dTMP, UTP and CTP.

33. Step 8
• UDP  dUDP by Ribonucleotide reductase
(thioredoxin-dependent reaction)
• dUDP + N5, N10-methylene tetrahydrofolate 
dTMP by “Thymidylate synthetase”dTMP by “Thymidylate synthetase”
• UDP + ATP  UTP by “kinase”
• UTP + Glutamine + ATP + H2O  CTP by “CTP
synthetase”