Nucleotide Biosynthesis

De novo and salvage pathways for purine and pyrimidine nucleotide production.

Overview

Purine nucleotides are synthesized de novo on a ribose-5-phosphate scaffold with contributions from amino acids, CO₂, and tetrahydrofolate. Pyrimidine nucleotides are built as free bases before attachment to ribose. Salvage pathways recycle preformed bases via HGPRT (purines) and thymidine kinase (pyrimidines). Ribonucleotide reductase converts ribonucleotides to deoxyribonucleotides for DNA synthesis.

Cellular Location

Cytoplasm

Clinical Significance

Essential for DNA/RNA synthesis and cell proliferation; targets of anticancer drugs (methotrexate, 5-FU, 6-MP) and immunosuppressants (mycophenolate, leflunomide).

Key Molecules

PRPP IMP AMP GMP UMP Orotate Ribose-5-phosphate THF (tetrahydrofolate)dNTPs

Key Enzymes

PRPP synthetase Amidophosphoribosyltransferase HGPRT Dihydroorotate dehydrogenase Ribonucleotide reductase Thymidylate synthase

Related Pathways

Pentose Phosphate Pathway

Generates NADPH and ribose-5-phosphate for biosynthesis.

Folate / One-Carbon Metabolism

Transfer of one-carbon units for nucleotide synthesis, methylation, and amino acid metabolism.