Nucleotide Metabolism

Roles of nucleotides in the cell:
1) Activated precursors of DNA and RNA
2) Nucleotide derivatives are activated intermediates in many biosynthetic pathways
e.g. UDP-glucose, CDP-diacylglycerol
3) Universal currency of cell (i.e. ATP)
4) Components of three major coenzymes: NAD+, FAD, and CoA
5) Metabolic regulators (i.e. cyclic AMP)
Nucleotide synthesis can either by de novoor by recycling preformed bases (salvage pathway).
Nomenclature:
Nucleotides are composed of three components:
1) nitrogenous base - pyrimidine (cytosine, uracil, thymine) or purine (adenine or guanine)
2) pentose sugar - ribose (RNA) or deoxyribose (DNA)
3) phosphate group
nucleoside - purine or pyrimidine base linked to pentose sugar
nucleotide - phosphate ester of nucleoside
SYNTHESIS OF PURINE NUCLEOTIDES
? Purine ring is synthesized de novo from 5 different precursors: aspartate (N-1 atom), CO2
(C-6 atom), glycine (C-4, C-5, N-7 atoms), tetrahydrofolate (C-2, C-8 atoms) and glutamine (
N-3, N-9).
? Purine ring structure is synthesized from ribose 5-phosphate; PRPP then donates ribose 5-
phosphate for purine synthesis.
? Purine ring is built onto the ribose 5-phosphate via a 10 -tep pathway: glutamine, glycine,
tetrahydrofolate, and glutamine make contributions to form 5-membered ring; construction
of 6-membered ring forms inosine 5’-monophosphate (IMP).
? IMP can be converted into AMP or GMP
? For AMP synthesis, aspartate amino group condenses with keto-group of IMP; GTPdependent reaction
? For GMP synthesis, C-2 is oxidized to form xanthosine monophosphate (XMP)
Amide nitrogen of glutamine replaces oxygen of C-2 to form GMP
ATP-dependent reaction
Synthesis of purine bases using the salvage pathway:
? Free purine bases are formed by degradation of nucleic acids and nucleotides.
? Purine nucleotides can be synthesized from preformed bases by salvage reactions (simpler
and less costly than de novopathway).