Nucleotide Degradation
Nucleotide Degradation
SCID
50X dATP
Gout is caused by an excess of uric acid
Uric acid
DNA and RNA in diet
Xanthine
Allopurinol
Xanthine oxidase
Elion and Hichings
1988 Nobel Prize
‘Rational design of drugs’
Purine Salvage Pathways
Adenine + PRPP
Guanine + PRPP
phosphoribosyltransferaseAMP + PPi
GMP + PPi
Lesch-Nyhan Syndrome
-increasing levels of PRPP in patients (male children) suffering from Lesch-Nyhan Syndrome leads to increased de novo purine biosynthetic pathways
-gout
-brain dependent upon salvage pathways
Nucleotide Metabolism and Chemotherapy
Glutamine Amidotransferase Inhibitors
Folate Analogs
Inhibitors of dTMP synthesis
Inhibitors of dTMP synthesis
Thymidylate synthase mechanism:
FdUMP is a suicide inhibitor of thymidylate synthase
1,3 hydride shift is blocked by the presence of Fluorine