Nucleotide metabolism 2024 notes

Page 1: Introduction to Biochemistry and Nucleotides

• Title: Biochemistry: Nucleotides Nucleotide Metabolism

Page 2: Functions of Nucleotides

1. Activated Precursors of Nucleic Acids:

   • Nucleotides are essential for genome replication and transcription to RNA.

2. Energy Currency:

   • ATP (adenine nucleotide) serves as the universal energy currency.

   • GTP (guanine nucleotide) acts as an energy source for specific biological processes.

3. Biosynthetic Processes:

   • Derivatives like UDP-glucose are vital for glycogen formation.

4. Signal Transduction:

   • Cyclic nucleotides (cAMP, cGMP) function as second messengers transducing signals.

5. Therapeutic Relevance:

   • Nucleotide biosynthesis pathways are critical targets for cancer therapies, with many drugs inhibiting these pathways.

Page 3: Nucleotide Biosynthesis Pathways

• Types of Pathways:

  • Nucleotide biosynthesis is categorized into de novo pathways and salvage pathways.

• De Novo Pathways:

  • Nucleotide bases are synthesized from simpler compounds.

  • Pyrimidine bases’ framework is assembled before attachment to ribose; purine bases assemble directly onto ribose.

• Salvage Pathways:

  • Involve recovery of preformed bases and their reconnection to ribose.

Page 4: Synthesis of Deoxyribonucleotides

• Conversion from Ribonucleotides:

  • DNA is derived from deoxyribonucleotides, synthesized from corresponding ribonucleotides.

  • Deoxyribose sugar is produced by reducing ribose within a nucleotide.

  • Methylation adds the distinguishing group of thymine over uracil at the final synthesis step.

• Degradation Products:

  • Breakdown of purine and pyrimidine nucleotides results in uric acid and urea.

Page 5: Differences in Synthesis Pathways

• Salvage vs. De Novo Pathways:

  • Salvage pathways reattach bases to ribose (using PRPP), while de novo synthesis builds bases from scratch.

Page 6: Overview of Synthesis Pathways

• Diagrams illustrating de novo pathways for pyrimidines and purines.

Page 7: Pyrimidine Synthesis (De Novo)

• Synthesis Route:

  • Pyrimidine rings formed from bicarbonate, aspartic acid, and ammonia.

  • Generally, ammonia originates from glutamine.

Page 8: Steps of Pyrimidine Biosynthesis

• Carbamoyl Phosphate Formation:

  • Generated from bicarbonate and glut

• The first step in de novo pyrimidine biosynthesis is the synthesis of carbamoyl phosphate from bicarbonate and glutamine (source of amino group) • Carbamoyl phosphate reacts with aspartate to form carbamoylaspartate • Carbamoylaspartate then cyclizes to form dihydroorotate which is then oxidized to form orotate • Orotate reacts with PRPP to form orotidylate, a pyrimidine nucleotide • Orotidylate is then decarboxylated to form uridylate (UMP), a major pyrimidine nucleotide that is a precursor to RNA • Nucleoside monophosphates are converted into nucleoside triphosphates in stages • First, nucleoside monophosphates are converted into diphosphates by specific nucleoside monophosphate kinases; e.g., UMP is phosphorylated to UDP by UMP kinase • Nucleoside diphosphates and triphosphates are interconverted by nucleoside diphosphate kinase • After uridine triphosphate has been formed, it can be transformed into cytidine triphosphate by the replacement of a carbonyl group by an amino