Nucleotide Synthesis

Basic Components

1. Nitrogenous base
2. Pentose sugar
3. Phosphate group

Nitrogenous Bases and Nucleotides

Purines

• Adenine (A)
  • When it binds with ribose and a phosphate, it is called adenosine monophosphate (AMP)
  • If it binds with deoxyribose, it is called deoxyadenosine monophosphate (dAMP)
• Guanine (G)
  • When it binds with ribose and a phosphate, it is called guanosine monophosphate (GMP)
  • If it binds with deoxyribose, it is called deoxyguanosine monophosphate (dGMP)

Pyrimidines

• Cytosine (C)
  • With ribose and phosphate: cytidine monophosphate (CMP)
  • With deoxyribose: deoxycytidine monophosphate (dCMP)
• Uracil (U)
  • With ribose: uridine monophosphate (UMP)
  • With deoxyribose (although rare in DNA): deoxyuridine monophosphate (dUMP)
• Thymine (T)
  • With deoxyribose: thymidine monophosphate (TMP)
  • Note: Thymine is found only in DNA

Pentose Sugar Synthesis

• Pentose phosphate pathway produces ribose 5-phosphate
  • Glucose 6-phosphate dehydrogenase converts glucose 6-phosphate to 6-phosphoglucono-δ-lactone
  • Lactonase converts 6-phosphoglucono-δ-lactone to 6-phosphogluconate
  • 6-phosphogluconate dehydrogenase converts 6-phosphogluconate to ribulose 5-phosphate
  • Ribose-5-phosphate isomerase converts ribulose 5-phosphate to ribose 5-phosphate
  • PRPP synthetase converts ribose 5-phosphate to PRPP (phosphoribosyl pyrophosphate)

Pyrimidine Synthesis

1. Carbamoyl phosphate synthetase II, glutamine, bicarbonate, ATP:
   • Produces carbamoyl phosphate
2. Aspartate transcarbamoylase:
   • Combines aspartate and carbamoyl phosphate to form carbamoyl aspartate
3. Dihydroorotase:
   • Dehydrates carbamoyl aspartate to form orotate
4. Orotate phosphoribosyl transferase:
   • Adds PRPP to orotate to form OMP (orotidine monophosphate)
5. OMP decarboxylase (orotidylate decarboxylase):
   • Converts OMP to UMP
6. UMP can be modified to UDP, UTP, and finally to CTP (cytosine triphosphate)
7. Ribonucleotide reductase:
   • Converts ribonucleotides to deoxyribonucleotides
8. Thymidylate synthase (with tetrahydrofolate):
   • Converts dUMP to dTMP

Purine Synthesis

1. PRPP, glutamine, bicarbonate, formate, glycine, aspartate:
   • Form IMP (inosine monophosphate)
2. IMP dehydrogenase:
   • Converts IMP to GMP (guanosine monophosphate)
3. GMP synthase:
   • Converts IMP to GMP
4. Adenylosuccinate synthetase, aspartate:
   • Forms adenylosuccinate
5. Adenylosuccinate lyase:
   • Converts adenylosuccinate to AMP
6. Ribonucleotide reductase:
   • Converts AMP and GMP to dAMP and dGMP