Nucleotide
Metabolism
Synthesis of
Purines & Pyrimidines

Ribose 5-P + ATP -----> PRPP

Enzyme PRPP Synthetase

PRPP + GLUTAMINE -------> IMP

Enzyme Glutamine Phophoribosyl Amino Transferase

IMP is "branch point" b/t ATP and GTP synthesis

IMP dehydrogenase

inhibited by mycophenolic acid

IMP + GTP + Aspartate ==> AMP

IMP + ATP + Glutamine ==> GMP

Purine Nucleotide Cycle in muscle cells

IMP + Aspartate ===> AMP + Fumarate

Releases NH3

Negative Feedback

GMP, GDP, & GTP inhibit--->AMP, ADP, & ATPinhibit--->

Glutamine phosphoribosyl amindotransferase

GMP inhibit -->

IMP dehydrogenase

AMP inhibits-->

Adenylosuccinate synthase

GDP and ADP inhibit -->

PRPP synthase

Via slavaging dietary nucleotides
Nucleotides ---> nucleosides

Adenine ---APRT----> AMP

when broken down = Kidney Stones

Hypoxanthine ------HGPRT-----> IMP

When broken down = Lesch–Nyhan Disease

Adenosine -------adenosine deaminase-------> Inosine

When broken down = SIDS
"bubble boy"

Inosine ---->Hypoxanthine -----> Xanthine -----Xanthine oxidase--------> Uric Acid

Allopurinol inhibits xanthine oxidase!
=> less uric acid --> less gout!

Nucleosides ----> uric acid

Excess uric acid ----> GOUT!

Ribonucleotide Reductase (RR)

Nucleotides -------> deoxynucleotides

Glutamine + CO2 + 2ATP ----> Carbamoyl Phosphate

Enzyme: (CPS-II)
Carbomoyl Phosphate Synthase II

NEG FeedbacK:
UTP

POS Feedback:
PRPP

Salvaging

Nucleotides ------phosphorylase-----> nucleosides

Cytosine ---> de-aminated ===> Uracil

Uracil --> CO2, NH4+ and beta-alanine

Thymine --> CO2, NH4+ and beta-aminoisobutyrate

ALL ARE water soluble
==> NO KIDNEY STONES