Hypoxanthine-guanine phosphoribosyltransferase

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is an is_associated_with::enzyme encoded in humans by the HPRT1 is_associated_with::gene.

HGPRT is a is_associated_with::transferase that catalyzes conversion of is_associated_with::hypoxanthine to is_associated_with::inosine monophosphate and is_associated_with::guanine to is_associated_with::guanosine monophosphate. This reaction transfers the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate (PRPP) to the purine. HGPRT plays a central role in the generation of is_associated_with::purine is_associated_with::nucleotides through the purine salvage pathway.

Function
HGPRT catalyzes the following reactions:

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

Substrates and inhibitors
Comparative homology modelling of this enzyme in is_associated_with::L. donovani suggest that among all of the computationally screened compounds, is_associated_with::pentamidine, 1,3-dinitrois_associated_with::adamantane, is_associated_with::acyclovir and analogs of acyclovir had higher binding affinities than the real substrate (guanosine monophosphate).

Role in disease
Mutations in the gene lead to is_associated_with::hyperuricemia:
 * Some men have partial (up to 20% less activity of the enzyme) HGPRT deficiency that causes high levels of is_associated_with::uric acid in the blood, which leads to the development of gouty arthritis and the formation of uric acid stones in the urinary tract. This condition has been named the is_associated_with::Kelley-Seegmiller syndrome.
 * is_associated_with::Lesch-Nyhan syndrome is due to deficiency of HGPRT caused by HPRT1 mutation
 * Some mutations have been linked to is_associated_with::gout, the risk of which is increased in hypoxanthine-guanine phosphoribosyltransferase deficiency.
 * HPRT expression on the mRNA and protein level is induced by hypoxia inducible factor 1 (is_associated_with::HIF1A). HIF-1 is a is_associated_with::transcription factor that directs an array of cellular responses that are used for adaptation during oxygen deprivation.  This finding implies that HPRT is a critical pathway that helps preserve the cell's is_associated_with::purine nucleotide resources under hypoxic conditions as found in pathology such as is_associated_with::myocardial ischemia.

Hybridomas
is_associated_with::Hybridomas are immortal (immune to is_associated_with::cellular senescence), HGPRT+ cells that result from fusion of mortal, HGPRT+ is_associated_with::plasma cells and immortal, HGPRT− is_associated_with::myeloma cells. They are created to produce is_associated_with::monoclonal antibodies in biotechnology. is_associated_with::HAT medium inhibits is_associated_with::de novo synthesis of nucleic acids, killing myelomas that cannot switch over to is_associated_with::salvage pathway, due to lack of HRPT1. Plasma cells eventually die from senesence, leaving pure hybridoma cells.