Chapter 22: Metabolism of Purine Nucleotides Flashcards
Principal/major purine bases
- Adenine
- Guanine
De novo synthesis of purine nucleotides
- Starting from scratch in the cytosol of the hepatocyte
De novo synthesis involves
- 10 steps
- Energy dependent pathway via IMP
- Primarily in liver
Two types of salvage reactions
- Phosphoribosylation
- Phosphorylation of purine nucleoides
Phosphoribosylation
- Adding a ribose-phosphate to an existing base (therefore, salvaging it)
Phosphorylation of purine nucleosides
- Adding a phosphate
- Requires less energy
Origins of the atoms of the purine ring
- Aspartate amine
- Formate
- Glutamine amide
- Formate
- Glycine
- HCO3-
De novo synthesis of purines is highly regulated and requires
- ATP
Starting material for de novo synthesis of purines
- Ribose-5-phosphate from PPP
Ribose-5-phosphate is converted to
- PRPP
Committed step of de novo synthesis
- PRPP glutamyl amidotransferase
GAR synthetase produces
- GAR
Cytoplasmic enzymes needed for IMP synthesis come from
- Ribose-5-phosphate
IMP is a common precursor of
- AMP
- GMP
IMP is
- The first purine nucleotide made
- Contains hypoxanthine
After IMP, the pathway branches to
- AMP and GMP
PRPP glutamyl amidotransferase is the committed step controlled by
- Negative feedback
Nucleoside monophosphates must be converted to
- Triphosphates by base-specific kinases
AMP + ATP is catalyzed by/converted to
- Adenylate kinase
- 2 ADP
GMP + ATP is catalyzed by/converted to
- Guanylate kinase
- GDP + ADP
GDP + ATP is catalyzed by/converted to
- Nucleoside diphosphate kinase
- GTP + ADP
Ribonucleotide reductase catalyzes the reduction of
- 2’ carbon of purine and pyrimidine diphosphates to deoxyribonucleotides (dNDPs) for DNA synthesis
Ribonucleotide reductase is inhibited by
- Methotrexate (anti-cancer)
Concentration of PRPP stimulates
- Purine nucleotide synthesis
