次黄嘌呤-鸟嘌呤磷酸核苷转移酶

hypoxanthine phosphoribosyltransferase
命名
系统命名
缩写
识别码
EC编号	2.4.2.8
CAS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

次黄嘌呤-鸟嘌呤磷酸核苷转移酶
识别号
别名	；HPRTinosinic pyrophosphorylaseinosinate pyrophosphorylaseinosinic acid pyrophosphorylaseinosine 5'-phosphate pyrophosphorylaseIMP:diphosphate phospho-D-ribosyltransferaseHGPRTaseIMP diphosphorylaseIMP pyrophosphorylaseIMP-GMP pyrophosphorylase
外部ID	GeneCards：[1]
直系同源
	无数据
	无数据
	无数据
	无数据
	无数据
	无数据
	无数据
	无数据
	无数据
	无数据
	维基数据
查看/编辑人类

次黄嘌呤-鸟嘌呤磷酸核苷转移酶（Hypoxanthine-guanine phosphoribosyltransferase，简称HGPRT）为人体内一个翻译自HPRT1基因的酵素^[1]^[2]

HGPRT为一种转移酶，可以催化将次黄嘌呤转换为肌苷酸（IMP），也可将鸟嘌呤的反应转为单磷酸鸟苷。这两个反应都是将PRPP的5-磷酸核苷转移至嘌呤上。HGPRT在核苷酸补救合成途径中扮演重要角色。

功能

HGPRT催化下列反应：

反应物	产物	备注
次黄嘌呤	肌苷酸	—
鸟嘌呤	单磷酸鸟苷	常称HGPRT，仅有部分物种有此功能。
黄嘌呤	单磷酸黄核苷（英语：xanthosine monophosphate）	特定HPRT

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（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

此基因的突变往往导致高尿酸血症：

一些男性带有部分程度的HGPRT缺陷（约低于正常活动量20%）并因此导致血液中高浓度的尿酸。随之而来的是痛风以及肾结石。这症状称为凯利-塞米勒综合征。^[4]
莱希-尼亨综合征起源由HPRT1突变导致的HGPRT缺陷。^[5]
某些基因突变可能导致痛风。发病的风险与hypoxanthine-guanine phosphoribosyltransferase的缺陷程度成正比。

透过基因工程让一只老鼠带有缺陷的HPRT基因后，老鼠的表现。

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

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.

参见

参考文献

^ 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-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.

延伸阅读

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.

外部链接

医学主题词表（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）

[Entrez-1] Entrez Gene: hypoxanthine phosphoribosyltransferase 1 (Lesch-Nyhan syndrome).

[pmid12175903-2] 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.

[pmid22327112-3] 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.

[pmid9651092-4] 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.

[pmid18779430-5] 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.

[pmid25681585-6] 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.

[pmid26616453-7] 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.

[1]

[2]

[3]

[4]

[5]

[6]

[7]