Purine Salvage Pathway

Hypoxanthine andAdenine

Hypoxanthine andAdenine

The biosynthesis of purine begins with ribose-5-phosphate, derived from pentose phosphate pathway (PPP).

First intermediate formed in this pathway, 5-phosphoribosyl-pyrophosphate (PRPP), is also an intermediate in purine salvage pathway.

Purine nucleotide synthesis occurs by two pathways :

1.De novo synthesis

2.Salvage pathway

Liver is the major site of purine nucleotide biosynthesis (de novo).

Certain tissues cannot synthesize purine nucleotides by de novo patyway, e g. brain, erythrocytes and polymor­phonuclear leukocytes.

These are dependent on salvage pathway for synthesis of purine nucleotides by using exogenous purines, which are formed by degradation of purine nucleotides synthesized in liver.

PRPP glutamyl amidotransferase is one of the rate limiting enzyme in de novo synthesis of purines. o The de novo synthesis of purines is most active in liver.

Brain, RBCs (erythrocytes) and polymorphonuclear leokocytes (polymorphs) cannot synthesize purine nucleotides by de novo pathway.

Biosynthesis of purine neucleotides

Two important purine nucleotides are synthesized : (i) adenosine monophosphate (AMP) and (ii) guanosine monophosphate (GMP). Then AMP and GMP are converted to other purine nucleotides like ADP, ATP, GDP, GTP etc. Purine nucleotides can be synthesized by two pathways – (I) De novo synthesis and (2) Salvage pathway.

De novo pathway (De novo synthesis)

In de novo pathway, the purine nucleotides are synthesized from amphibolic intermediates. Amphibolic intermediates are the intermediary metabolites of amphibolic pathways (eg. citric acid cycle) which have dual purposes, i e. they serve in catabolism as well as in anabolism.

In de novo synthesis, purine ring is formed from variety of precursors is assembled on ribose-5-phosphate. Precursors for de novo synthesis are ‑

i)  Glycine provides C4 C5 and N7

ii)  Aspartate provides NI

iii)  Glutamine provides N3 and N9

iv)  Tetrahydrofolate derivatives furnish C2 and Cs

v)  Carbon dioxide provides C6

Purine nucleotide synthesis occurs by two pathways :-

1.De novo synthesis

2.Salvage pathway

Liver is the major site of purine nucleotide biosynthesis (de novo).

Certain tissues cannot synthesize purine nucleotides by de novo patyway, e g. brain, erythrocytes and polymorphonuclear leukocytes.

These are dependent on salvage pathway for synthesis of purine nucleotides by using exogenous purines, which are formed by degradation of purine nucleotides synthesized in liver.