Lect 9 Nucleotide Metabolism Flashcards
Nucleoside
Base + Sugar
Nucleotide
Base + Sugar + Phosphate
Purines
Pure As Gold (Ring)
Double Ring
Adenine & Guanine
Xanthine & Hypothanxine
Pyrimidine
CUt The Pye
Single Ring
Cytosine & Thymine
Uracil
What are 3 Roles of Nucleosides and Nucleotides
Components of Cofactors
Regulatory Roles
Important biomolecules
What is the overall Purine Nucelotide Synthesis process?
Sugar Molecule Synthesis —> Ring Formation
What occurs in Purine synthesis Phase I?
What enzyme is used?
Ribose 5P Activation
Ribose 5P –> PRPP/Phosphoribosyl pyrophosphate
(PRPP Synthetase)
Purine Phase II
What is the enzyme?
Why is this step special?
Convert PRPP to PRA (Phosphoribosylamine)
Glutamine Phosphoribosyl Pyrophosphate Amidotransferase (GPPA)
Rate Limiting Step
Purine Phase III
Why is methotrexate an inhibitor?
Why is it an anticancer drug?
Construct IMP Ring (PRA –> IMP in 9 Steps)
Methotrexate inhibits (competitive) oxidation of NADPH by DHFR/Dihyrofolate Reductase
Methotrexate: Competitive Inhibitor of enzymes utilizing folate (disrupts DNA replication in rapidly dividing cell)
Purine Phase IV
Convert IMP to AMP and GMP
What are Sulfa Drugs and what are their importance?
Competitive inhibitors of bacterial enzyme incorporating PABA into folate
Dirsupts DNA replication selectivley in bacteria
Feeback Inhibition
Purine inhibition example
Accumulation of end product inhibit own synthesis
PRPP: inhibitted by IMP, AMP, GMP
Cross Regulation
Synthesis is stimulated by production of other substrate
AMP synthesis stimulated by GTP
GMP stimulated by ATP
Pyrimidine Nucleotide Synthesis Overall View
Pyrimidine Ring Formation –> Sugar Attachment
Sources: HCO3-, Gln, Asp, N, N-methylene THF
Cytosol and Mitochondria
What does Pyrimidine Synthesis Phase I consist of?
What is the rate limiting step?
Formation of the orotate ring –> Committed Step
Carbamoyl phosphate + Asp –> carbamoyl aspartate via aspartate transcarbamoylase