PURINE AND

PYRIMIDINE
METABOLISM

Purine Synthesis

Purine Synthesis

Purine Synthesis

Purine Synthesis

Purine Salvage Pathway

Lesch-Nyhan sindrome
Associated with a virtually complete
deficiency of hypoxanthineguanine
phosphoribosyltransferase and, therefore,
the inability to salvage hypoxanthine or
guanine.
Results in increased levels of PRPP and
decreased levels of IMP and GMP, causing
increased de novo purine synthesis.
This results in the excessive production of
uric acid, plus characteristic neurologic
features, including selfmutilation and
involuntary movements.

Purine Degradation

Pyrimidine synthesis

Unlike the synthesis of the purine ring which is formed by a pre-existing ribose 5phosphate, the pyrimidine ring is synthesized before being attached to ribose 5-phosphate
which is donated by PRPP.

PRPP: 5-Phosphoribosil 1 pyrophosphate, a form of ribose activated to accept nucleotide

bases.

Summary

Base built first, the attached to PRPP

Requires Gln, Asp, CO2

Product is UMP (the other pyrimidine

nucleotides are formed from UMP)

Degradation and salvage of pyrimidines

Unlike the purine ring, which is not cleaved by humans, the pyrimidine ring
is opened and degrated to highly soluble products:

B-alanine (from degradation of CMP and UMP)

B-aminoisobutyrate ( from TMP degradation).

Pyrimidines can be salvaged to nucleosides with the production of NH3 and

CO2

Orotic Aciduria
Autosomal recessive.
This disorder usually appears during the first years of life and is
characterized by growth failure, developmental retardation,
megaloblastic anemia and increased urinary excretion of orotic
acid
Inability to convert orotic acid to UMP (de novo pyrimidine
synthesis pathway) because of defect in UMP synthase.
UMP is the precursor for UTP, CTP and TMP. All of these end
products act in some way to feedback inhibt the initial reactions
of pyrimidine synthesis. Especially the lack of CTP inhibition
allows Aspartate transcarmoylase to remain highly active. This
results in over production of orotic acid which gets accumulated
and excreted in urine excessively
Treatment: uridine is effective because it can be easily converted
to UMP thus allowing UTP, CTP and TMP to be synthesized and
feedback inhibit further Orotic acid production..

THANKS