BIOC/DENT/PHCY 230

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BIOC/DENT/PHCY 230 LECTURE 6
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Nucleotides

• found in DNA and RNA
• used for energy (ATP and GTP)
• building blocks for coenzymes (NADH)

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Building blocks for nucleotides
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Two classes of bases
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Two types of ribose
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Synthesis of nucleotides

• nucleotide bases can be recycled or synthesised
  de novo
• purine bases are synthesised on ribose
• pyrimidine bases are synthesisedindependent of
  ribose

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Synthesis of PRPP

• PRPP contributes ribose phosphate to
  nucleotides
• formation catalysed by PRPP synthetase

PRPP synthetase is allosterically inhibited by
AMP, ADP and GDP.
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De novo purine synthesis
Glutamine donates an amide to initiate purine
synthesis
A whole glycine is added to the nitrogen
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The coenzyme tetrahydrofolate donates a formyl
group
Glutamine donates a second amide
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Imidazole ring is closed in an energy dependent
reaction
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Aspartate is added in an energy dependent
reaction This is analogous to the urea cycle
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Ring closure
Tetrahydrofolate donates a second formyl group
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Origins of purine base
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IMP can be converted to GMP and AMP
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De novo pyrimidine synthesis
The pyrimidine base is synthesised before being
attached to ribose
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ring closure and oxidation
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Ribose is now added via PRPP
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UMP can be used to synthesise CTP
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Origins of pyrimidine base
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Comparison of purine and pyrimidine biosynthesis
CMP gln 3
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Ribonucleotides are used as precursors for
deoxyribonucleotides
ATP dATP GTP dGTP CTP dCTP UTP dUTP
Ribonucleotide reductase
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Thymidine nucleotides are derived from dUMP
Tetrahydrofolate donates a methyl group
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Degradation of pyrimidine nucleotides
CTP UTP
b-alanine, NH3, CO2
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Degradation of purine nucleotides
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Free ammonia is also produced in muscle

• during severe muscle activity

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Degradation of purine nucleotides
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GOUT

• uric acid is quite insoluble
• excess uric acid can crystallise in joints
• gout can be treated with allopurinol
• allopurinol is a competitive inhibitor of
  xanthine oxidase

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The take home message

• nucleotides have a number of functions
• they can be synthesised de novo if required
• some steps are analogous with the urea cycle
• amino acids provide many of the components
• synthesis is regulated by the concentrations of
  various nucleotides
• synthesis is energetically expensive
• the degradation of excess purines can cause gout