Lecture Notes: Synthesis of Nucleotides - Purine and Pyrimidine Synthesis

Basic Components of Nucleotides

• Nitrogenous Base
  • Focus of the lecture
  • Examples: Adenine, Guanine (Purines) and Cytosine, Uracil, Thymine (Pyrimidines)
• Pentose Sugars
  • Can be deoxyribose or ribose
• Phosphate Groups

Naming Conventions

• Purines
  • Adenine becomes adenosine monophosphate (AMP) when combined with ribose sugar and a phosphate.
  • Guanine becomes guanosine monophosphate (GMP) when similarly combined.
  • For deoxy versions, add 'deoxy' (e.g., deoxyadenosine monophosphate is dAMP).
• Pyrimidines
  • Cytosine becomes cytidine monophosphate (CMP).
  • Uracil becomes uridine monophosphate (UMP).
  • Thymine becomes thymidine monophosphate (TMP).
  • Deoxy versions for DNA include dCMP, dUMP, and dTMP.

Pentose Phosphate Pathway

• Conversion of glucose to ribose-5-phosphate via glucose-6-phosphate.
• Key enzymes:
  • Glucose 6-phosphate dehydrogenase
  • Lactamase
  • Ribose phosphate pyrophosphokinase (PRPP)
• Outcome: Production of ribose-5-phosphate and deoxyribose.

Pyrimidine Synthesis

• Begins with glutamine, bicarbonate, and ATP to form carbamoyl phosphate.
• Enzymes:
  • Carbamoyl phosphate synthetase II
  • Aspartate transcarbamoylase
  • Dihydratase
• Formation of orotate and subsequent conversion to orotidine monophosphate (OMP).
• Conversion of OMP to UMP and eventually to CTP.
• Enzyme for UMP to CTP: Nucleoside diphosphate kinase

Deoxyribonucleotide Synthesis

• Ribonucleotide reductase converts ribonucleotides to deoxyribonucleotides.
• Example: Conversion from UMP to dUMP

Thymidine Synthesis

• dUMP is converted to dTMP via thymidylate synthase using tetrahydrofolate.

Purine Synthesis

• Inputs: PRPP, glutamine, bicarbonate, formate, glycine, and aspartate.
• Key intermediate: Inosine monophosphate (IMP)
• Conversion of IMP to AMP and GMP using specific enzymes.
• Enzyme for GMP synthesis: GMP synthase
• Conversion of AMP to deoxy form using ribonucleotide reductase.

Conclusion

• Understanding these pathways is crucial for DNA and RNA synthesis.
• Each nucleotide has specific pathways and enzymes facilitating its synthesis.
• Importance of enzymes like ribonucleotide reductase and thymidylate synthase in these processes.