Salvage Pathways for Pyrimidine and Purine
Denovo Synthesis of Nucleotides is Expensive in terms
of the use of high energy phosphate bonds esp. for
All tissues are not capable of denovo synthesis of Purine
nucleotides such as Erythrocytes, Neutrophils,
They lack PRPP Amido
Purine Salvage Pathway
Two Pathways available.
I. One step Synthesis
Formation of GMP and IMP
Hypoxanthine Guanine Phosphoribosyltransferase (HGPRT)
catalyses the One step nucleotide formation from either
Guanine or Hypoxanthine using PRPP as the donor of ribosyl
Guanine Similarly, Hypoxanthine
PRPP HGPRT HGPRT
GMP + PPi Inosine + PPi
II. Two Step Synthesis
Nucleoside Phosphorylase- Nucleoside
Adenine + Ribose-1-P
Adenosine + Pi
AMP + ADP
Neither Guanosine nor Inosine Kinase has been detected in mammalian cells.
In addition to the above cycle, there is another salvage cycle for
purines GMP, IMP as well as their deoxyribonucleotides which
is converted to their respective nucleosides by a PURINE-
Rare, X-linked, recessive disorder.
Virtually complete deficiency of HGPRT.
Results in an inability to salvage hypo -
xanthine or guanine, from which excessive
amounts of uric acid is produced.
Lack of the salvage pathway causes
increased PRPP levels and decreased IMP
and GMP levels.
Denovopurine synthesis is increased.
Combination of decreased purine
reutilization and increased purine synthesis
results in increased degradation of purines
and the production of large amounts of uric
acid, making Lesch-Nyhan a heritable
cause of hyperuricemia.
Hyperuricemia frequently results in the
formation of uric acid stones in the kidneys
(urolithiasis) and the deposition of urate
crystals in the joints (gouty arthritis) and
Syndrome is also characterized by motor
dysfunction, cognitive deficits, and
behavioral disturbances that include self-
mutilation (biting of lips and fingers)
Pyrimidine Base Salvage
Pyrimidine Phosphoribosyl Transferase catalyses the formation
of Pyrimidine Nucleotide using PRPP.
Pyrimidine Phosphoribosyl Transfersae
Pyrimidine Nucleotide + PPi
Catabolism of Purines
Adenine and Guanine nucleotides are converted to various
compounds catalyzed by their respective enzymes until the
final common product Xanthine is produced.
A. Adenine Nucleotide Metabolism
In Liver and Heart Muscle
Purine 5’- Nucleotidase
I. AMP Adenosine
II. Adenosine Inosine
Purine Nucleoside Phosphorylase
III. Inosine Ribose-1-P
IV. Hypoxanthine Xanthine
In Skeletal Muscle:
I. AMP Adenylate Deaminase IMP
Purine 5’- Nucleotidase
II. IMP Inosine
III. Inosine Uric Acid
Released from Thymidine or produced from deamination of 5- “
NADPH dependent dehydrogenase
CO2, NH3, Beta aminoisobutyrate