Hypoxanthine-guanine phosphoribosyltransferase


Hypoxanthine-guanine phosphoribosyltransferase is an enzyme encoded in humans by the HPRT1 gene.
HGPRT is a transferase that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate. This reaction transfers the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate to the purine. HGPRT plays a central role in the generation of purine nucleotides through the purine salvage pathway.

Function

HGPRT catalyzes the following reactions:
SubstrateProductNotes
hypoxanthineinosine monophosphate—
guanineguanosine monophosphateOften called HGPRT. Performs this function only in some species.
xanthinexanthosine monophosphateOnly certain HPRTs.

HGPRTase functions primarily to salvage purines from degraded DNA to reintroduce into purine synthetic pathways. In this role, it catalyzes the reaction between guanine and phosphoribosyl pyrophosphate to form GMP, or between hypoxanthine and phosphoribosyl pyrophosphate to form inosine monophosphate.

Substrates and inhibitors

Comparative homology modelling of this enzyme in L. donovani suggest that among all of the computationally screened compounds, pentamidine, 1,3-dinitroadamantane, acyclovir and analogs of acyclovir had higher binding affinities than the real substrate.
The in silico and in-vitro correlation of these compounds were test in Leishmania HGPRT and validates the result.

Role in disease

Mutations in the gene lead to hyperuricemia:
s are immortal, HGPRT+ cells that result from fusion of mortal, HGPRT+ plasma cells and immortal, HGPRT− myeloma cells. They are created to produce monoclonal antibodies in biotechnology. HAT medium inhibits de novo synthesis of nucleic acids, killing myeloma cells that cannot switch over to the salvage pathway, due to lack of HPRT1. The plasma cells in the culture eventually die from senescence, leaving pure hybridoma cells.