Comparative homology modelling of this enzyme in L. donovani（英语：L. donovani） suggest that among all of the computationally screened compounds, pentamidine（英语：pentamidine）, 1,3-dinitroadamantane, acyclovir and analogs of acyclovir had higher binding affinities than the real substrate (guanosine monophosphate).[3]
HPRT expression on the mRNA and protein level is induced by hypoxia inducible factor 1 (HIF1A（英语：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.[6]
Hybridoma（英语：Hybridoma）s are immortal (immune to cellular senescence（英语：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（英语：HAT medium） inhibits de novo synthesis of nucleic acids, killing myeloma cells that cannot switch over to the salvage pathway, due to lack of HRPT1. The plasma cells in the culture eventually die from senesence, leaving pure hybridoma cells.
^Finette BA, Kendall H, Vacek PM. Mutational spectral analysis at the HPRT locus in healthy children. Mutation Research. Aug 2002, 505 (1-2): 27–41. PMID 12175903. doi:10.1016/S0027-5107(02)00119-7.
^Ansari MY, Dikhit MR, Sahoo GC, Das P. Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP. International Journal of Biological Macromolecules. Apr 2012, 50 (3): 637–49. PMID 22327112. doi:10.1016/j.ijbiomac.2012.01.010.
^Khattak FH, Morris IM, Harris K. Kelley-Seegmiller syndrome: a case report and review of the literature. British Journal of Rheumatology. May 1998, 37 (5): 580–1. PMID 9651092. doi:10.1093/rheumatology/37.5.580c.
^Hladnik U, Nyhan WL, Bertelli M. Variable expression of HPRT deficiency in 5 members of a family with the same mutation. Archives of Neurology. Sep 2008, 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, Wright G. HIF-1α in the heart: Remodeling nucleotide metabolism. Journal of Molecular and Cellular Cardiology. Feb 2015, 82: 194–200. PMID 25681585. doi:10.1016/j.yjmcc.2015.01.014.
^Ansari MY, Equbal A, Dikhit MR, Mansuri R, Rana S, Ali V, Sahoo GC, Das P. Establishment of Correlation between In-Silico &In-Vitro Test Analysis against Leishmania HGPRT to inhibitors. International Journal of Biological Macromolecules. Nov 2015, 83: 78–96. PMID 26616453. doi:10.1016/j.ijbiomac.2015.11.051.
延伸閱讀
Sculley DG, Dawson PA, Emmerson BT, Gordon RB. A review of the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Human Genetics. Nov 1992, 90 (3): 195–207. PMID 1487231. doi:10.1007/bf00220062.
Ansari MY, Dikhit MR, Sahoo GC, Das P. Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP. International Journal of Biological Macromolecules. Apr 2012, 50 (3): 637–49. PMID 22327112. doi:10.1016/j.ijbiomac.2012.01.010.
Davidson BL, Tarlé SA, Van Antwerp M, Gibbs DA, Watts RW, Kelley WN, Palella TD. Identification of 17 independent mutations responsible for human hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. American Journal of Human Genetics. May 1991, 48 (5): 951–8. PMC 1683055. PMID 2018042.
Stout JT, Caskey CT. HPRT: gene structure, expression, and mutation. Annual Review of Genetics. 1986, 19: 127–48. PMID 3909940. doi:10.1146/annurev.ge.19.120185.001015.
Sege-Peterson K, Chambers J, Page T, Jones OW, Nyhan WL. Characterization of mutations in phenotypic variants of hypoxanthine phosphoribosyltransferase deficiency. Human Molecular Genetics. Sep 1992, 1 (6): 427–32. PMID 1301916. doi:10.1093/hmg/1.6.427.
Lightfoot T, Joshi R, Nuki G, Snyder FF. The point mutation of hypoxanthine-guanine phosphoribosyltransferase (HPRTEdinburgh) and detection by allele-specific polymerase chain reaction. Human Genetics. Mar 1992, 88 (6): 695–6. PMID 1551676. doi:10.1007/BF02265300.
Yamada Y, Goto H, Ogasawara N. Identification of two independent Japanese mutant HPRT genes using the PCR technique. Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology. 1992, 309B: 121–4. ISBN 978-1-4615-7705-8. PMID 1840476. doi:10.1007/978-1-4615-7703-4_27.
Sculley DG, Dawson PA, Beacham IR, Emmerson BT, Gordon RB. Hypoxanthine-guanine phosphoribosyltransferase deficiency: analysis of HPRT mutations by direct sequencing and allele-specific amplification. Human Genetics. Oct 1991, 87 (6): 688–92. PMID 1937471. doi:10.1007/BF00201727.
Tarlé SA, Davidson BL, Wu VC, Zidar FJ, Seegmiller JE, Kelley WN, Palella TD. Determination of the mutations responsible for the Lesch-Nyhan syndrome in 17 subjects. Genomics. Jun 1991, 10 (2): 499–501. PMID 2071157. doi:10.1016/0888-7543(91)90341-B.
Gordon RB, Sculley DG, Dawson PA, Beacham IR, Emmerson BT. Identification of a single nucleotide substitution in the coding sequence of in vitro amplified cDNA from a patient with partial HPRT deficiency (HPRTBRISBANE). Journal of Inherited Metabolic Disease. 1991, 13 (5): 692–700. PMID 2246854. doi:10.1007/BF01799570.
Edwards A, Voss H, Rice P, Civitello A, Stegemann J, Schwager C, Zimmermann J, Erfle H, Caskey CT, Ansorge W. Automated DNA sequencing of the human HPRT locus. Genomics. Apr 1990, 6 (4): 593–608. PMID 2341149. doi:10.1016/0888-7543(90)90493-E.
Gibbs RA, Nguyen PN, Edwards A, Civitello AB, Caskey CT. Multiplex DNA deletion detection and exon sequencing of the hypoxanthine phosphoribosyltransferase gene in Lesch-Nyhan families. Genomics. Jun 1990, 7 (2): 235–44. PMID 2347587. doi:10.1016/0888-7543(90)90545-6.
Skopek TR, Recio L, Simpson D, Dallaire L, Melancon SB, Ogier H, O'Neill JP, Falta MT, Nicklas JA, Albertini RJ. Molecular analyses of a Lesch-Nyhan syndrome mutation (hprtMontreal) by use of T-lymphocyte cultures. Human Genetics. Jun 1990, 85 (1): 111–6. PMID 2358296. doi:10.1007/BF00276334.
Davidson BL, Tarlé SA, Palella TD, Kelley WN. Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in ten subjects determined by direct sequencing of amplified transcripts. The Journal of Clinical Investigation. Jul 1989, 84 (1): 342–6. PMC 303988. PMID 2738157. doi:10.1172/JCI114160.
Ogasawara N, Stout JT, Goto H, Sonta S, Matsumoto A, Caskey CT. Molecular analysis of a female Lesch-Nyhan patient. The Journal of Clinical Investigation. Sep 1989, 84 (3): 1024–7. PMC 329751. PMID 2760209. doi:10.1172/JCI114224.
Yang TP, Stout JT, Konecki DS, Patel PI, Alford RL, Caskey CT. Spontaneous reversion of novel Lesch-Nyhan mutation by HPRT gene rearrangement. Somatic Cell and Molecular Genetics. May 1988, 14 (3): 293–303. PMID 2835825. doi:10.1007/BF01534590.
Fujimori S, Hidaka Y, Davidson BL, Palella TD, Kelley WN. Identification of a single nucleotide change in a mutant gene for hypoxanthine-guanine phosphoribosyltransferase (HPRT Ann Arbor). Human Genetics. May 1988, 79 (1): 39–43. PMID 2896620. doi:10.1007/BF00291707.
Davidson BL, Pashmforoush M, Kelley WN, Palella TD. Human hypoxanthine-guanine phosphoribosyltransferase deficiency. The molecular defect in a patient with gout (HPRTAshville). The Journal of Biological Chemistry. Jan 1989, 264 (1): 520–5. PMID 2909537.
Fujimori S, Davidson BL, Kelley WN, Palella TD. Identification of a single nucleotide change in the hypoxanthine-guanine phosphoribosyltransferase gene (HPRTYale) responsible for Lesch-Nyhan syndrome. The Journal of Clinical Investigation. Jan 1989, 83 (1): 11–3. PMC 303636. PMID 2910902. doi:10.1172/JCI113846.
GeneReviews/NCBI/NIH/UW entry on Lesch-Nyhan Syndrome （页面存档备份，存于互联网档案馆）
Category:EC 2.4.2（英语：Category:EC 2.4.2）
一月 26, 2023
次黃嘌呤, 鳥嘌呤磷酸核苷轉移酶, hypoxanthine, guanine, phosphoribosyltransferase, 簡稱hgprt, 為人體內一個轉譯自hprt1基因的酵素, 識別號别名, hprtinosinic, pyrophosphorylaseinosinate, pyrophosphorylaseinosinic, acid, pyrophosphorylaseinosine, phosphate, pyrophosphorylaseimp, diphosphate, phospho,. 次黃嘌呤 鳥嘌呤磷酸核苷轉移酶 Hypoxanthine guanine phosphoribosyltransferase 簡稱HGPRT 為人體內一個轉譯自HPRT1基因的酵素 1 2 次黃嘌呤 鳥嘌呤磷酸核苷轉移酶識別號别名 HPRTinosinic pyrophosphorylaseinosinate pyrophosphorylaseinosinic acid pyrophosphorylaseinosine 5 phosphate pyrophosphorylaseIMP diphosphate phospho D ribosyltransferaseHGPRTaseIMP diphosphorylaseIMP pyrophosphorylaseIMP GMP pyrophosphorylase外部IDGeneCards 1 直系同源物種人類小鼠Entrez无数据无数据Ensembl无数据无数据UniProt无数据无数据mRNA 序列无数据无数据蛋白序列无数据无数据基因位置 UCSC 无数据无数据PubMed 查找无数据无数据維基數據檢視 編輯人類HGPRT為一種轉移酶 可以催化將次黃嘌呤轉換為肌苷酸 IMP 也可將鳥嘌呤的反應轉為單磷酸鳥苷 這兩個反應都是將PRPP的5 磷酸核苷轉移至嘌呤上 HGPRT在核苷酸再利用合成途徑中扮演重要角色 目录 1 功能 2 Substrates and inhibitors 3 疾病中的角色 4 Hybridomas 5 參見 6 參考文獻 7 延伸閱讀 8 外部連結功能 编辑hypoxanthine phosphoribosyltransferase命名系统命名缩写识别码EC編號 2 4 2 8CAS号 9016 12 0数据库IntEnz IntEnz浏览BRENDA 英语 BRENDA BRENDA入口ExPASy 英语 ExPASy NiceZyme浏览KEGG KEGG入口MetaCyc 英语 MetaCyc 代谢路径PRIAM 英语 PRIAM enzyme specific profiles 概述PDB RCSB PDB PDBj PDBe PDBsum基因本体 AmiGO EGO搜索PMC 相关文献PubMed 相关文献HGPRT催化下列反應 反應物 產物 備註次黃嘌呤 肌苷酸 鳥嘌呤 單磷酸鳥苷 常稱HGPRT 僅有部分物種有此功能 黄嘌呤 單磷酸黃核苷 英语 xanthosine monophosphate 特定HPRTHGPRTase 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 编辑Comparative homology modelling of this enzyme in L donovani 英语 L donovani suggest that among all of the computationally screened compounds pentamidine 英语 pentamidine 1 3 dinitroadamantane acyclovir and analogs of acyclovir had higher binding affinities than the real substrate guanosine monophosphate 3 疾病中的角色 编辑此基因的突變往往導致高尿酸血症 一些男性帶有部分程度的HGPRT缺陷 約低於正常活動量20 並因此導致血液中高濃度的尿酸 隨之而來的是痛風以及腎結石 這症狀稱為凱利 塞米勒症候群 4 萊希 尼亨症候群起源由HPRT1突變導致的HGPRT缺陷 5 某些基因突變可能導致痛風 發病的風險與hypoxanthine guanine phosphoribosyltransferase的缺陷程度成正比 source source source source source source source source source source 透過基因工程讓一隻老鼠帶有缺陷的HPRT基因後 老鼠的表現 HPRT expression on the mRNA and protein level is induced by hypoxia inducible factor 1 HIF1A 英语 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 6 The in silico and in vitro correlation of these compounds were test in Leishmania HGPRT and validates the result 7 Hybridomas 编辑Hybridoma 英语 Hybridoma s are immortal immune to cellular senescence 英语 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 英语 HAT medium inhibits de novo synthesis of nucleic acids killing myeloma cells that cannot switch over to the salvage pathway due to lack of HRPT1 The plasma cells in the culture eventually die from senesence leaving pure hybridoma cells 參見 编辑參考文獻 编辑 Entrez Gene hypoxanthine phosphoribosyltransferase 1 Lesch Nyhan syndrome Finette BA Kendall H Vacek PM Mutational spectral analysis at the HPRT locus in healthy children Mutation Research Aug 2002 505 1 2 27 41 PMID 12175903 doi 10 1016 S0027 5107 02 00119 7 Ansari MY Dikhit MR Sahoo GC Das P Comparative modeling of HGPRT enzyme of L donovani and binding affinities of different analogs of GMP International Journal of Biological Macromolecules Apr 2012 50 3 637 49 PMID 22327112 doi 10 1016 j ijbiomac 2012 01 010 Khattak FH Morris IM Harris K Kelley Seegmiller syndrome a case report and review of the literature British Journal of Rheumatology May 1998 37 5 580 1 PMID 9651092 doi 10 1093 rheumatology 37 5 580c Hladnik U Nyhan WL Bertelli M Variable expression of HPRT deficiency in 5 members of a family with the same mutation Archives of Neurology Sep 2008 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 Wright G HIF 1a in the heart Remodeling nucleotide metabolism Journal of Molecular and Cellular Cardiology Feb 2015 82 194 200 PMID 25681585 doi 10 1016 j yjmcc 2015 01 014 Ansari MY Equbal A Dikhit MR Mansuri R Rana S Ali V Sahoo GC Das P Establishment of Correlation between In Silico amp In Vitro Test Analysis against Leishmania HGPRT to inhibitors International Journal of Biological Macromolecules Nov 2015 83 78 96 PMID 26616453 doi 10 1016 j ijbiomac 2015 11 051 延伸閱讀 编辑Sculley DG Dawson PA Emmerson BT Gordon RB A review of the molecular basis of hypoxanthine guanine phosphoribosyltransferase HPRT deficiency Human Genetics Nov 1992 90 3 195 207 PMID 1487231 doi 10 1007 bf00220062 Ansari MY Dikhit MR Sahoo GC Das P Comparative modeling of HGPRT enzyme of L donovani and binding affinities of different analogs of GMP International Journal of Biological Macromolecules Apr 2012 50 3 637 49 PMID 22327112 doi 10 1016 j ijbiomac 2012 01 010 Davidson BL Tarle SA Van Antwerp M Gibbs DA Watts RW Kelley WN Palella TD Identification of 17 independent mutations responsible for human hypoxanthine guanine phosphoribosyltransferase HPRT deficiency American Journal of Human Genetics May 1991 48 5 951 8 PMC 1683055 PMID 2018042 Stout JT Caskey CT HPRT gene structure expression and mutation Annual Review of Genetics 1986 19 127 48 PMID 3909940 doi 10 1146 annurev ge 19 120185 001015 Sege Peterson K Chambers J Page T Jones OW Nyhan WL Characterization of mutations in phenotypic variants of hypoxanthine phosphoribosyltransferase deficiency Human Molecular Genetics Sep 1992 1 6 427 32 PMID 1301916 doi 10 1093 hmg 1 6 427 Lightfoot T Joshi R Nuki G Snyder FF The point mutation of hypoxanthine guanine phosphoribosyltransferase HPRTEdinburgh and detection by allele specific polymerase chain reaction Human Genetics Mar 1992 88 6 695 6 PMID 1551676 doi 10 1007 BF02265300 Yamada Y Goto H Ogasawara N Identification of two independent Japanese mutant HPRT genes using the PCR technique Advances in Experimental Medicine and Biology Advances in Experimental Medicine and Biology 1992 309B 121 4 ISBN 978 1 4615 7705 8 PMID 1840476 doi 10 1007 978 1 4615 7703 4 27 Sculley DG Dawson PA Beacham IR Emmerson BT Gordon RB Hypoxanthine guanine phosphoribosyltransferase deficiency analysis of HPRT mutations by direct sequencing and allele specific amplification Human Genetics Oct 1991 87 6 688 92 PMID 1937471 doi 10 1007 BF00201727 Tarle SA Davidson BL Wu VC Zidar FJ Seegmiller JE Kelley WN Palella TD Determination of the mutations responsible for the Lesch Nyhan syndrome in 17 subjects Genomics Jun 1991 10 2 499 501 PMID 2071157 doi 10 1016 0888 7543 91 90341 B Gordon RB Sculley DG Dawson PA Beacham IR Emmerson BT Identification of a single nucleotide substitution in the coding sequence of in vitro amplified cDNA from a patient with partial HPRT deficiency HPRTBRISBANE Journal of Inherited Metabolic Disease 1991 13 5 692 700 PMID 2246854 doi 10 1007 BF01799570 Edwards A Voss H Rice P Civitello A Stegemann J Schwager C Zimmermann J Erfle H Caskey CT Ansorge W Automated DNA sequencing of the human HPRT locus Genomics Apr 1990 6 4 593 608 PMID 2341149 doi 10 1016 0888 7543 90 90493 E Gibbs RA Nguyen PN Edwards A Civitello AB Caskey CT Multiplex DNA deletion detection and exon sequencing of the hypoxanthine phosphoribosyltransferase gene in Lesch Nyhan families Genomics Jun 1990 7 2 235 44 PMID 2347587 doi 10 1016 0888 7543 90 90545 6 Skopek TR Recio L Simpson D Dallaire L Melancon SB Ogier H O Neill JP Falta MT Nicklas JA Albertini RJ Molecular analyses of a Lesch Nyhan syndrome mutation hprtMontreal by use of T lymphocyte cultures Human Genetics Jun 1990 85 1 111 6 PMID 2358296 doi 10 1007 BF00276334 Davidson BL Tarle SA Palella TD Kelley WN Molecular basis of hypoxanthine guanine phosphoribosyltransferase deficiency in ten subjects determined by direct sequencing of amplified transcripts The Journal of Clinical Investigation Jul 1989 84 1 342 6 PMC 303988 PMID 2738157 doi 10 1172 JCI114160 Ogasawara N Stout JT Goto H Sonta S Matsumoto A Caskey CT Molecular analysis of a female Lesch Nyhan patient The Journal of Clinical Investigation Sep 1989 84 3 1024 7 PMC 329751 PMID 2760209 doi 10 1172 JCI114224 Yang TP Stout JT Konecki DS Patel PI Alford RL Caskey CT Spontaneous reversion of novel Lesch Nyhan mutation by HPRT gene rearrangement Somatic Cell and Molecular Genetics May 1988 14 3 293 303 PMID 2835825 doi 10 1007 BF01534590 Fujimori S Hidaka Y Davidson BL Palella TD Kelley WN Identification of a single nucleotide change in a mutant gene for hypoxanthine guanine phosphoribosyltransferase HPRT Ann Arbor Human Genetics May 1988 79 1 39 43 PMID 2896620 doi 10 1007 BF00291707 Davidson BL Pashmforoush M Kelley WN Palella TD Human hypoxanthine guanine phosphoribosyltransferase deficiency The molecular defect in a patient with gout HPRTAshville The Journal of Biological Chemistry Jan 1989 264 1 520 5 PMID 2909537 Fujimori S Davidson BL Kelley WN Palella TD Identification of a single nucleotide change in the hypoxanthine guanine phosphoribosyltransferase gene HPRTYale responsible for Lesch Nyhan syndrome The Journal of Clinical Investigation Jan 1989 83 1 11 3 PMC 303636 PMID 2910902 doi 10 1172 JCI113846 外部連結 编辑醫學主題詞表 MeSH Hypoxanthine phosphoribosyltransferase Purine metabolism at genome jp 页面存档备份 存于互联网档案馆 GeneReviews NCBI NIH UW entry on Lesch Nyhan Syndrome 页面存档备份 存于互联网档案馆 Category EC 2 4 2 英语 Category EC 2 4 2 取自 https zh wikipedia org w index php title 次黃嘌呤 鳥嘌呤磷酸核苷轉移酶 amp oldid 69456156, 维基百科，wiki，书籍，书籍，图书馆，
