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次黃嘌呤-鳥嘌呤磷酸核苷轉移酶

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hypoxanthine phosphoribosyltransferase
識別號
別名;HGPRTase、​HPRT、​IMP diphosphorylase、​IMP pyrophosphorylase、​IMP-GMP pyrophosphorylase、​IMP:diphosphate phospho-D-ribosyltransferase、​inosinate pyrophosphorylase、​inosine 5'-phosphate pyrophosphorylase、​inosinic acid pyrophosphorylase、​inosinic pyrophosphorylase
外部IDGeneCards[1]
直系同源
物種人類小鼠
Entrez
Ensembl
UniProt
mRNA​序列

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蛋白序列

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基因位置​(UCSC)n/an/a
PubMed​查找n/an/a
維基資料
檢視/編輯 人類

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基因酵素[1][2]

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。

功能[編輯]

hypoxanthine phosphoribosyltransferase
識別碼
EC編號 2.4.2.8
CAS號 9016-12-0
資料庫
IntEnz IntEnz瀏覽
BRENDA英語BRENDA BRENDA入口
ExPASy英語ExPASy NiceZyme瀏覽
KEGG KEGG入口
MetaCyc英語MetaCyc 代謝路徑
PRIAM英語PRIAM_enzyme-specific_profiles 概述
PDB RCSB PDB PDBj PDBe PDBsum
基因本體 AmiGO / EGO

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。
黃嘌呤 單磷酸黃核苷英語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[編輯]

Comparative homology modelling of this enzyme in L. donovani英語L. donovani suggest that among all of the computationally screened compounds, pentamidine英語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[編輯]

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。
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英語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[編輯]

Hybridoma英語Hybridomas are immortal (immune to cellular senescence英語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英語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[編輯]

參考文獻[編輯]

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

延伸閱讀[編輯]

外部連結[編輯]

Category:EC 2.4.2英語Category:EC 2.4.2