Nucleotide Metabolism Flashcards
Purine bases
- Adenine
- Guanine
- Hypoxanthine
- Xanthine
Pyrimidine bases
- Uracil
- Cytosine
- Thymine
PRPP Synthesis
- From ribose-5-phosphate and ATP
- Catalyzed by PRPP Synthetase
Sources of ribose-5-phosphate
- Glucose metab, pentose phosphate shunt
- Nucleoside degradation creates R1P which can be converted
PRPP is required for:
- Purine and pyrimidine nucleotide de novo synthesis
- Salvage pathways for purine nucleotides
- Biosynthesis of NAD and FAD
Synthesis of purine nucleotides
- Purine ring built on PRPP
- Precursors are glutamine, glycine, CO2, aspartate, and two 1 carbon fragments from one-carbon folate pool (THF)
Sulfonamides
- Block the biosynthesis of folate by bacteria
- Blocks two steps in the production of IMP that require folate
Components of IMP nucleotide ring
-Glutamine, glycine, CO2, aspartate, two one carbon fragments from the one-carbon folate pool
Azaserine
- Analog of glutamine that blocks amide transfer from glutamine
- Interferes with two steps in IMP production that require glutamine transfer reactions
Energy cost of making IMP
-Six high energy phosphate bonds
Formation of AMP from IMP
- Adenylosuccinate formed by addition of aspartate to IMP
- Fumarate cleaved to yield AMP
- GTP cleaved in the process
Formation of GMP from IMP
- XMP formed by oxidation of IMP
- Amino group from glutamine added to form GMP
- ATP cleaved in the process
HGPRT
- Catalyzes formation of NTs from hypoxanthine or guanine (forms IMP and GMP respectively)
- Salvage pathway
- Uses PRPP
APRT
- Catalyzes formation of AMP from adenosine
- Salvage pathway
- Uses PRPP
Nucleoside kinase
- Salvage pathway only for adenosine
- Forms AMP and ADP using ATP
Synthesis of pyrimidine nucleotides
- NOT built on PRPP. Synthesized first and then reacts with PRPP to form nucleotide
- Precursors are carbamoylphosphate and aspartate