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 Purines

• Adenine = 6-amino purine

• Guanine = 2-amino-6-oxy
purine

• Hypoxanthine = 6-oxy
purine

• Xanthine = 2,6-dioxy
purine

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 Pyrimidines

• Uracil = 2,4-dioxy
pyrimidine
• Thymine = 2,4-dioxy-5-
methyl pyrimidine
• Cytosine = 2-oxy-4-
amino pyrimidine
• Orotic acid = 2,4-dioxy-
6-carboxy pyrimidine

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 Medical relevance of nucleotide
pathways
Critical in cancer treatment

Hydroxyurea, anti-folates, FdUMP, 5-FU, etc

Antiviral therapies

acyclovir and herpes

Important inborn errors and pathologies

Adenosine deaminase and SCIDS

Lesch-Nyhan Syndrome

Hyperuricemia

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 Lesch-Nyhan syndrome

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 Orotic aciduria
• an inherited human disease caused by a
deficiency in the multifunctional enzyme
that catalyzes the last 2 steps in the
pyrimidine synthesis
• large amounts of orotic acid in urine
• retarded growth and severe anemia
• treat by administration (injection) of uridine
and/or cytidine

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 CLINICAL SIGNIFICANCE
6-Mercaptopurine Inhibits PRPP Amidotransferase, IMP DHASE,
Adenylsuccinate synthase
5-Fluorouracil(FUTP) Inhibit maturation of r,m RNA
(FdUMP) Inhibits thymidylate synthase
Methotrexate Inhibits H2 folate reductase.
Azaserine : Inhibits enzymes that utilize gln as N doners
(Gln antagonists)
6-Diazo-5-oxo-1-norleucine: “
(Gln antagonists)
Hydroxyurea: Inhibits ribonuleotide reductase.
3-azido-3-deoxythymidine -AZT :antiviral-chain termination
(pyr analog)
Acycloguanosine- Acyclovir: "
( pur. Analog)

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