HGPRTase functions primarily to salvage purines from degraded DNA to reintroduce into purine synthetic pathways. In this role, catalyzes in the reaction between guanine and phosphoribosyl pyrophosphate (PRPP) to form GMP.
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).
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.
B cells contain this enzyme, which enables them to survive when fused to myeloma cells when grown on HAT medium to produce monoclonal antibodies. The antibodies are produced from cells called hybridoma cells. A hybridoma, which can be considered as a hybrid cell, is produced by the injection of a specific antigen into a mouse, procuring the antibody-producing cell from the mouse's spleen and the subsequent fusion of this cell with a cancerous immune cell called a myeloma cell. The hybrid cell, which is thus produced, can be cloned to produce many identical daughter clones. These daughter clones then secrete the immune cell product.
The method of selecting hybridomas is by use of HAT medium, which contain hypoxanthine, aminopterin, and thymidine. The aminopterin inhibits enzyme dihydrofolate reductase (DHFR), which is necessary in the de novo synthesis of nucleic acids. Thus, the cell is left with no other option but to use the alternate salvage pathway, which utilises HGPRT. In the HAT medium, HGPRT- cell lines will die, as they cannot synthesise nucleic acids through salvage pathway. Only HGPRT+ cells will survive in presence of aminopterin, which are the hybridoma cells and plasma cells. The plasma cells eventually die as they are mortal cell lines, thus only hybridoma cells are left surviving. The hybrid cell (hybridoma cell) can be cloned to produce many identical daughter clones. These daughter clones subsequently secrete the monoclonal antibody product.
^Ansari MY, Dikhit MR, Sahoo GC, Das P (April 2012). "Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP". Int. J. Biol. Macromol.50 (3): 637–49. doi:10.1016/j.ijbiomac.2012.01.010. PMID22327112.
^Hladnik U, Nyhan WL, Bertelli M (September 2008). "Variable expression of HPRT deficiency in 5 members a family with the same mutation". Arch. Neurol.65 (9): 1240–3. doi:10.1001/archneur.65.9.1240. PMID18779430.
Sculley DG, Dawson PA, Emmerson BT, Gordon RB (1993). "A review of the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency". Hum. Genet.90 (3): 195–207. PMID1487231.
Ansari MY, Dikhit MR, Sahoo GC, Das P. (2012). "Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP". Int J Biol Macromol.50 (3): 637–49. doi:10.1016/j.ijbiomac.2012.01.010. PMID22327112.Unknown parameter |unused_data= ignored (help)
Sculley DG, Dawson PA, Beacham IR, et al. (1991). "Hypoxanthine-guanine phosphoribosyltransferase deficiency: analysis of HPRT mutations by direct sequencing and allele-specific amplification". Hum. Genet.87 (6): 688–92. doi:10.1007/BF00201727. PMID1937471.
Gordon RB, Sculley DG, Dawson PA, et al. (1991). "Identification of a single nucleotide substitution in the coding sequence of in vitro amplified cDNA from a patient with partial HPRT deficiency (HPRTBRISBANE)". J. Inherit. Metab. Dis.13 (5): 692–700. doi:10.1007/BF01799570. PMID2246854.
Gibbs RA, Nguyen PN, Edwards A, et al. (1990). "Multiplex DNA deletion detection and exon sequencing of the hypoxanthine phosphoribosyltransferase gene in Lesch-Nyhan families". Genomics7 (2): 235–44. doi:10.1016/0888-7543(90)90545-6. PMID2347587.
Skopek TR, Recio L, Simpson D, et al. (1990). "Molecular analyses of a Lesch-Nyhan syndrome mutation (hprtMontreal) by use of T-lymphocyte cultures". Hum. Genet.85 (1): 111–6. doi:10.1007/BF00276334. PMID2358296.
Yang TP, Stout JT, Konecki DS, et al. (1988). "Spontaneous reversion of novel Lesch-Nyhan mutation by HPRT gene rearrangement". Somat. Cell Mol. Genet.14 (3): 293–303. doi:10.1007/BF01534590. PMID2835825.
Fujimori S, Hidaka Y, Davidson BL, et al. (1988). "Identification of a single nucleotide change in a mutant gene for hypoxanthine-guanine phosphoribosyltransferase (HPRT Ann Arbor)". Hum. Genet.79 (1): 39–43. doi:10.1007/BF00291707. PMID2896620.
Davidson BL, Pashmforoush M, Kelley WN, Palella TD (1989). "Human hypoxanthine-guanine phosphoribosyltransferase deficiency. The molecular defect in a patient with gout (HPRTAshville)". J. Biol. Chem.264 (1): 520–5. PMID2909537.