Purine Metabolism

Dr. Bishal Raj Joshi

Assistant Professor
Department of Biochemistry
Objectives
• Understand the structure of purine molecules.
• Know the different types of pathway of purine synthesis and specific organs
and subcellular location of these pathways.
• Know what are the contributors of different atoms of purine molecule.
• Understand the importance of de novo and salvage pathways.
• Know the regulatory steps in purine synthesis and understand how purine
synthesis is regulated.
• With the exception of parasitic protozoa, all forms of life synthesize
purine and pyrimidine nucleotides.
• The purine nucleotides are synthesized by most of the tissues.
However the major site is the liver. This pathway operates in the
cytoplasm.
• Two ways of synthesis:
De Novo Synthesis
Salvage pathway
De Novo synthesis
Activation of ribose 5-phosphate
Salvage Pathway
• This pathway ensures the recycling of purines formed by degradation of
nucleotides. Nucleosides and deoxy-nucleosides can also be salvaged.
• Human brain tissue, erythrocytes and polymorphonuclear leukocytes utilize
exogenous purines to form nucleotides (has low level or lack of PRPP glutamyl
amidotransferase).

Two salvage mechanisms:

Purine + PRPP  Pu-RP + PPi
Pu-R + ATP  PuR-P + ADP
Salvage
pathway
Regulation of purine metabolism
• The committed step in de novo synthesis is the
reaction catalyzed by amido-transferase. It is
inhibited by AMP and GMP. They act as allosteric
modifiers. Binding of AMP and GMP on the
enzyme converts monomeric active form to a
dimeric inactive form. Since both AMP and GMP
can bind to the same enzyme molecule at
different sites, they act synergistically.
• Both AMP and GMP inhibit their own
formation by feedback inhibition of
adenylosuccinate synthetase and IMP
dehydrogenase.
• The formation of AMP from IMP requires
GTP; similarly formation of GMP requires
ATP. Hence both GTP and ATP are made
available in sufficient quantities.
Formation of deoxyribonucleotides
Are these fulfilled??
• Understand the structure of purine molecules.
• Know the different types of pathway of purine synthesis and specific organs
and subcellular location of these pathways.
• Know what are the contributors of different atoms of purine molecule.
• Understand the importance of de novo and salvage pathways.
• Know the regulatory steps in purine synthesis and understand how purine
synthesis is regulated.
The correct sequence of de novo synthesis of
purine is:
•Glutamine

•Glycine

•N10 formyl THF

•Glutamine

•Ring closure (Imidazole)

•CO2

•Aspartate

•N10 formyl THF

•Ring closure (formation of IMP)

Thank You