Nucleotide Metabolism Outline
Notes HERE
Salvage vs. de novo pathway (HERE)
Nomenclature (HERE)
Structures (figures in this section are not in the PowerPoint file)
Pyrimidine Synthesis
- de novo scheme (HERE)
- Carbamoyl phosphate formation (HERE and HERE)
- Carbamoyl phosphate synthetase substrate channeling (HERE)
- Formation of Orotate (HERE)
- Formation of PRPP (HERE)
- Formation of Orotidylate (HERE)
- Formation of Uridylate (HERE)
- UMP + ATP <=> UDP + ADP (Nucleoside monophosphate kinases)
- XDP + YTP <=> XTP + YTP (Nucleoside diphosphate kinase)
- Formation of CTP from UTP (HERE)
Purine Synthesis
- de novo scheme (HERE)
- Pathway to inosinate (HERE)
- Inosinate to AMP & GMP (HERE)
- Salvage
- Adenine + PRPP <=> Adenylate + PPi (Adenine phosphoribosyl transferase)
- Guanine + PRPP <=> Guanylate + PPi (Hypoxanthine-guanine phosphoribosyltransferase - HGPRT)
- Hypoxanthine + PRPP <=> Inosinate + PPi (HGPRT)
dNTP Synthesis
Ribonucleotide reductase
- Action scheme (HERE)
- Overall structure - R1 dimer + R2 dimer (HERE)
- R2 (small) subunit (HERE)
- Reaction mechanism (HERE and HERE)
- Thymidylate synthesis (HERE)
- Dihydrofolate reductase (HERE)
- Anticancer drug targets (HERE)
- Aminopterin/Methotrexate (HERE)
- Trimethoprim (HERE)
Nucleotide Synthesis Regulation
- ATCase feedback inhibition of pyrimidine synthesis (HERE)
- Control of purine synthesis (HERE)
- Regulation of dNTP synthesis by ribonucleotide reductase (HERE)
Nucleotide catabolism
- SCID and adenosine deaminase deficiency (HERE)
- Hypoxanthine -> xanthine -> uric acid crystals (Gout) (HERE)
- Allopurinol treatment
- Suicide inhibitor of xanthine oxidase
- Lesch-Nyhan syndrome
- Deficiency of Hypoxanthine-guanine phosphoribosyltransferase - HGPRT and accumulation of PRPP and urate
- Folic acid deficiency promotes spinal bifida
- 70% reduction when supplemented in mother's diet
