Nucleotide
Metabolism
Synthesis of
Purines & Pyrimidines
Pyrimidine
Production
Degradation
ALL ARE water soluble
==> NO KIDNEY STONES
Thymine --> CO2, NH4+ and beta-aminoisobutyrate
Uracil --> CO2, NH4+ and beta-alanine
Cytosine ---> de-aminated ===> Uracil
Production
Salvaging
Nucleotides ------phosphorylase-----> nucleosides
Glutamine + CO2 + 2ATP ----> Carbamoyl Phosphate
Enzyme: (CPS-II)
Carbomoyl Phosphate Synthase II
POS Feedback:
PRPP
NEG FeedbacK:
UTP
Purine
production
Ribonucleotide Reductase (RR)
Regulation:
Nucleotides -------> deoxynucleotides
Nucleosides ----> uric acid
Excess uric acid ----> GOUT!
Via slavaging dietary nucleotides
Nucleotides ---> nucleosides
Inosine ---->Hypoxanthine -----> Xanthine -----Xanthine oxidase--------> Uric Acid
Allopurinol inhibits xanthine oxidase!
=> less uric acid --> less gout!
Adenosine -------adenosine deaminase-------> Inosine
When broken down = SIDS
"bubble boy"
Hypoxanthine ------HGPRT-----> IMP
When broken down = Lesch–Nyhan Disease
Adenine ---APRT----> AMP
when broken down = Kidney Stones
Negative Feedback
GDP and ADP inhibit -->
PRPP synthase
AMP inhibits-->
Adenylosuccinate synthase
GMP inhibit -->
GMP, GDP, & GTP inhibit--->AMP, ADP, & ATPinhibit--->
Glutamine phosphoribosyl amindotransferase
Purine Nucleotide Cycle in muscle cells
Releases NH3
IMP + Aspartate ===> AMP + Fumarate
IMP + ATP + Glutamine ==> GMP
IMP + GTP + Aspartate ==> AMP
PRPP + GLUTAMINE -------> IMP
IMP dehydrogenase
inhibited by mycophenolic acid
IMP is "branch point" b/t ATP and GTP synthesis
Enzyme Glutamine Phophoribosyl Amino Transferase
Ribose 5-P + ATP -----> PRPP
Enzyme PRPP Synthetase
