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Nucleotide Biosynthesis

Nucleotide Biosynthesis. nucleotides is essential for life processes. nucleotides are the activated precursors of nucleic acids. As such, they are necessary for the replication of the genome

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Nucleotide Biosynthesis

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  1. Nucleotide Biosynthesis

  2. nucleotides is essential for life processes • nucleotides are the activated precursors of nucleic acids. As such, they are necessary for the replication of the genome • an adenine nucleotide, ATP, is the universal currency of energy. A guanine nucleotide, GTP, also serves as an energy source for a more select group of biological processes. • Third, nucleotide derivatives such as UDP-glucose participate in biosynthetic processes such as the formation of glycogen. • nucleotides are essential components of signal-transduction pathways. cyclic AMP and cyclic GMP are second messengers that transmit signals both within and between cells.

  3. RNA & DNA

  4. RNA & DNA

  5. Two Purines Adenine Guanine Two Pyrimidines Thymine/Uracil Cytosine Purines and Pyrimidines

  6. Salvage Pathway de novo Pathway Synthesis Pathways • For both purines and pyrimidines there are two means of synthesis (often regulate one another) • de novo (from bits and parts) • salvage (recycle from pre-existing nucleotides)

  7. Many Steps Require an Activated Ribose Sugar (PRPP) 5’

  8. X de novo Synthesis • Committed step: This is the point of no return • Occurs early in the biosynthetic pathway • Often regulated by final product (feedback inhibition)

  9. Biosynthesis of Pyrimidines • Synthesized from: • Glutamine • CO2 • Aspartic acid • Requires ATP Uracil Cytosine • Pyrimidine rings are synthesized independent of the ribose and transferred to the PRPP (ribose) • Generated as UMP (uridine 5’-monophosphate)

  10. DENOVO Synthesis of Pyrimidine

  11. DENOVO Synthesis of Pyrimidine 1. Bicarbonate and Other Oxygenated Carbon Compounds Are Activated by Phosphorylation 2. Orotate Acquires a Ribose Ring from PRPP to Form a PyrimidineNucleotideand Is Converted into Uridylate

  12. DENOVO Synthesis of Pyrimidine 3. CTP is Formed by Amination of UTP

  13. DENOVO Synthesis of Pyrimidine

  14. X Inhibited by AMP, GMP, IMP Purine Biosynthesis (de novo) • Atoms derived from: • Aspartic acid • Glycine • Glutamine • CO2 • Tetrahydrofolate • Also requires • 4 ATP’s Committed Step Purines are synthesized on the Ribose ring

  15. DENOVO Synthesis of Purine

  16. DENOVO Synthesis of Purine

  17. DENOVO Synthesis of Purine

  18. Salvage Pathway for Purines Hypoxanthine or Guanine + PRPP = IMP or GMP + PPi Hypoxanthineguanosylphosphoribosyl transferase (HGPRTase) Adenine + PRPP = AMP + PPi Adeninephosphoribosyl transferase (APRTase)

  19. Biosynthesis: Purine vs Pyrimidine Purine Pyrimidine • Synthesized on PRPP • Regulated by GTP/ATP • Generates IMP • Requires Energy • Synthesized then added to PRPP • Regulated by UTP • Generates UMP/CMP • Requires Energy Both are very complicated multi-step process which your kindly professor does not expect you to know in detail

  20. Please VISITwww.reactome.com

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