Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) 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 (PRPP) to the purine. HGPRT plays a central role in the generation of purine nucleotides through the purine salvage pathway.
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 guanine and phosphoribosyl pyrophosphate (PRPP) to form GMP, or between hypoxanthine and phosphoribosyl pyrophosphate (PRPP) 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 (guanosine monophosphate).
Role in disease
Mutations in the gene lead to hyperuricemia:
- Some men have partial (up to 20% less activity of the enzyme) HGPRT deficiency that causes high levels of 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 Kelley-Seegmiller syndrome.
- Lesch-Nyhan syndrome is due to deficiency of HGPRT caused by HPRT1 mutation 
- Some mutations have been linked to 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 (HIF1A). HIF-1 is a 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 purine nucleotide resources under hypoxic conditions as found in pathology such as myocardial ischemia.
Hybridomas are immortal (immune to cellular senescence), 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 myelomas that cannot switch over to salvage pathway, due to lack of HRPT1. Plasma cells eventually die from senesence, leaving pure hybridoma cells.
- ↑ "Entrez Gene: hypoxanthine phosphoribosyltransferase 1 (Lesch-Nyhan syndrome)".
- ↑ Finette BA, Kendall H, Vacek PM (Aug 2002). "Mutational spectral analysis at the HPRT locus in healthy children". Mutation Research 505 (1-2): 27–41. PMID 12175903. doi:10.1016/S0027-5107(02)00119-7.
- ↑ Ansari MY, Dikhit MR, Sahoo GC, Das P (Apr 2012). "Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP". International Journal of Biological Macromolecules 50 (3): 637–49. PMID 22327112. doi:10.1016/j.ijbiomac.2012.01.010.
- ↑ Khattak FH, Morris IM, Harris K (May 1998). "Kelley-Seegmiller syndrome: a case report and review of the literature". British Journal of Rheumatology 37 (5): 580–1. PMID 9651092. doi:10.1093/rheumatology/37.5.580c.
- ↑ Hladnik U, Nyhan WL, Bertelli M (Sep 2008). "Variable expression of HPRT deficiency in 5 members of a family with the same mutation". Archives of Neurology 65 (9): 1240–3. PMID 18779430. doi:10.1001/archneur.65.9.1240.
- ↑ Wu J, Bond C, Chen P, Chen M, Li Y, Shohet RV et al. (Feb 2015). "HIF-1α in the heart: Remodeling nucleotide metabolism". Journal of Molecular and Cellular Cardiology. PMID 25681585. doi:10.1016/j.yjmcc.2015.01.014.
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- Ansari MY, Dikhit MR, Sahoo GC, Das P (Apr 2012). "Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP". International Journal of Biological Macromolecules 50 (3): 637–49. PMID 22327112. doi:10.1016/j.ijbiomac.2012.01.010.
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