Purine/Pyrimidine Metabolism Flashcards
PRPP Synthesis
- Reactant
- Enzyme
- Other substrates
Ribose-5-phosphate —> PRPP
- PRPP Synthase/ Ribose Phosphate
Pyrophosphokinase - ATP —> AMP
What is the role of PRPP Glutamine Amidotranferase? How is it controlled?
- Takes amino group from Glutamine and converts PRPP to Phosphoribosylamine
Allosterically regulated:
Positive: PRPP
Negative: IMP, AMP, GMP
What is the action of Mercaptopurine?
Inhibits PRPP amidotranferase
What pathway is Phosphoribosylamine committed to?
De Novo Purine synthesis
What enzyme is used to build purines from Phosphoribosylamine? What other reactants are used?
GAR Synthase
- Gly
- ATP
After GAR Synthase, what reaction occurs in De novo purine synthesis of IMP?
A charged THF is used to transfer a formal group
What high energy molecules are needed for production of AMP/GMP?
AMP: requires GTP
GMP: requires ATP
Describe how IMP is used to produce AMP
IMP —> Adenylosuccinate —> AMP
- Adenylosuccinate Synthetase
- Uses Asp + GTP
- 2nd step releases Fumarate
Describe how IMP is used to produce GMP.
IMP —> XMP —> GMP
Step 1: IMP DH
- Uses H2O, NAD+ -> NADH
Step 2: XMP-GLNG Amidotranferase
- Gln -> Glu
- ATP —> AMP + PPi
What are the various origins of the different parts of a purine molecule?
- N3/9 —> Glutamine
- C2/8 —> Formyl Group
- C6 —> BiCarb Keto
- N1 —> Aspartate
- C4/5, N7 —> Glycine
What is the importance of folate in nucleic acid synthesis?
- Folate needed to produce THF
- THF important for 1 carbon units transfers —> Amino acids and nucleic acid synthesis
*N10 Formyl THF in NA synthesis
What is used to detoxify methanol poisoning?
Folate
What two drugs interact with THF production?
Sulfonamides: inhibits folate production
Trimethoprim: Inhibits DHFR Which Conversion DHF to THF
What enzymes are used for Purine Salvage?
HGPRT (Guanine breakdown)
APRT (Adenine Breakdown)
What enzyme can also break down a nucleic acid to IMP?
HGPRT
What is the significance of the salvage pathways?
RBCs —> No nuclei —-> Rely on salivate pathways
What does NDPK catalyze?
Conversion of all nucleoside diphosphates to triphosphates
What are the three components of Folate?
- PABA
- Pteridine ring
- Glutamate