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.
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.
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^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 Neurology65 (9): 1240–3. doi:10.1001/archneur.65.9.1240. PMID18779430.
^Wu J, Bond C, Chen P, Chen M, Li Y, Shohet RV, Wright G (Feb 2015). "HIF-1α in the heart: Remodeling nucleotide metabolism". Journal of Molecular and Cellular Cardiology. doi:10.1016/j.yjmcc.2015.01.014. PMID25681585.
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