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Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is an enzyme encoded in humans by the HPRT1 gene.^[1]^[2]

HGPRT is a transferase that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate. This reaction transfers the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate to the purine. HGPRT plays a central role in the generation of purine nucleotides through the purine salvage pathway.

Function[edit]

HGPRT catalyzes the following reactions:

Substrate	Product	Notes
hypoxanthine	inosine monophosphate	—
guanine	guanosine monophosphate	Often called HGPRT. Performs this function only in some species.
xanthine	xanthosine monophosphate	Only certain HPRTs.

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.

Substrates and inhibitors[edit]

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).^[3]

Role in disease[edit]

Mutations in the gene lead to hyperuricemia:

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.^[4]
Lesch-Nyhan syndrome is due to HPRT mutations resulting in extremely ineffective enzyme activity.^[5]
Some mutations have been linked to gout, the risk of which is increased in hyperuricemia.

Application to hybridomas[edit]

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.

References[edit]

^ "Entrez Gene: hypoxanthine phosphoribosyltransferase 1 (Lesch-Nyhan syndrome)".
^ Finette BA, Kendall H, Vacek PM (August 2002). "Mutational spectral analysis at the HPRT locus in healthy children". Mutat. Res. 505 (1–2): 27–41. doi:10.1016/S0027-5107(02)00119-7. PMID 12175903.
^ 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. PMID 22327112.
^ Khattak FH, Morris IM, Harris K (May 1998). "Kelley-Seegmiller syndrome: a case report and review of the literature". Br. J. Rheumatol. 37 (5): 580–1. doi:10.1093/rheumatology/37.5.580c. PMID 9651092.
^ Hladnik U, Nyhan WL, Bertelli M (September 2008). "Variable expression of HPRT deficiency in 5 members of a family with the same mutation". Arch. Neurol. 65 (9): 1240–3. doi:10.1001/archneur.65.9.1240. PMID 18779430.

External links[edit]

Hypoxanthine phosphoribosyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)
Purine metabolism at genome.jp
GeneReviews/NCBI/NIH/UW entry on Lesch-Nyhan Syndrome

UpToDate Contents

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1. 炎症性腸疾患におけるアザチオプリンおよび6-メルカプトプリン azathioprine and 6 mercaptopurine in inflammatory bowel disease
2. 尿酸による腎疾患 uric acid renal diseases
3. リウマチ性疾患に使用した場合のアザチオプリンの薬理作用および副作用 pharmacology and side effects of azathioprine when used in rheumatic diseases
4. 免疫グロブリンの機能および臨床応用 function and clinical applications of immunoglobulins
5. 小児における運動過多な運動障害 hyperkinetic movement disorders in children

English Journal

PfHPRT: a new biomarker candidate of acute Plasmodium falciparum infection.

Thézénas ML, Huang H, Njie M, Ramaprasad A, Nwakanma DC, Fischer R, Digleria K, Walther M, Conway DJ, Kessler BM, Casals-Pascual C.AbstractPlasmodium falciparum is a protozoan parasite that causes human malaria. This parasitic infection accounts for approximately 655,000 deaths each year worldwide. Most deaths could be prevented by diagnosing and treating malaria promptly. To date, few parasite proteins have been developed into rapid diagnostic tools. We have combined a shotgun and a targeted proteomic strategy to characterize the plasma proteome of Gambian children with severe malaria (SM), mild malaria and convalescent controls in search of new candidate biomarkers. Here we report four P. falciparum proteins with a high level of confidence in SM patients, namely PF10_0121 (Hypoxanthine phosphoribosyltransferase, pHPRT), PF11_0208 (Phosphoglycerate mutase, pPGM), PF13_0141 (Lactate dehydrogenase, pLDH), and PF14_0425 (Fructose bisphosphate aldolase, pFBPA). We have optimized selected reaction monitoring (SRM) assays to quantify these proteins in individual patients. All P. falciparum proteins were higher in SM compared with mild cases or control subjects. SRM-based measurements correlated markedly with clinical anemia (low blood hemoglobin concentration), and pLDH and pFBPA were significantly correlated with higher P. falciparum parasitemia. These findings suggest that pHPRT is a promising biomarker to diagnose P. falciparum malaria infection. The diagnostic performance of this marker should be validated prospectively.
Journal of proteome research.J Proteome Res.2013 Jan 22. [Epub ahead of print]
Plasmodium falciparum is a protozoan parasite that causes human malaria. This parasitic infection accounts for approximately 655,000 deaths each year worldwide. Most deaths could be prevented by diagnosing and treating malaria promptly. To date, few parasite proteins have been developed into rapid d
PMID 23339668

ALDH16A1 is a novel non-catalytic enzyme that may be involved in the etiology of gout via protein-protein interactions with HPRT1.

Vasiliou V, Sandoval M, Backos DS, Jackson BC, Chen Y, Reigan P, Lanaspa MA, Johnson RJ, Koppaka V, Thompson DC.SourceDepartment of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora CO 80045 USA.
Chemico-biological interactions.Chem Biol Interact.2013 Jan 21. pii: S0009-2797(13)00006-9. doi: 10.1016/j.cbi.2012.12.018. [Epub ahead of print]
Gout, a common form of inflammatory arthritis, is strongly associated with elevated uric acid concentrations in the blood (hyperuricemia). A recent study in Icelanders identified a rare missense single nucleotide polymporphism (SNP) in the ALDH16A1 gene, ALDH16A1∗2, to be associated with gout and
PMID 23348497

Japanese Journal

HPRT部分欠損症の妊娠女性例に対する遺伝カウンセリング

井野口卓,森脇優司,高橋澄夫,堤善多,華常祥,玉置橋本知子,山本徹也
痛風と核酸代謝 = Gout and nucleic acid metabolism 33(2), 171-175, 2009-12-01
NAID 10026427008

Radiation-quality Dependent Cellular Response in Mutation Induction in Normal Human Cells

SUZUKI Masao,TSURUOKA Chizuru,UCHIHORI Yukio,KITAMURA Hisashi,LIU Cui Hua
Journal of radiation research 50(5), 395-399, 2009-09-16
… In mutation induction, which was detected in the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus to measure 6-thioguanine resistant clones, there was no difference in mutation frequency induced by the X-ray challenging dose between unpretreated and gamma-ray pretreated cells. …
NAID 10025912493

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拡張検索	「hypoxanthine phosphoribosyltransferase gene mutation」
関連記事	「phosphoribosyltransferase」

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hypoxanthine phosphoribosyltransferase
Identifiers
EC number	2.4.2.8
CAS number	9016-12-0
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
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PMC	articles
PubMed	articles
NCBI	proteins

Hypoxanthine phosphoribosyltransferase 1
	; Ribbon diagram of a human HPRT tetramer. Magnesium ions visible in green. From PDB 1BZY.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1BZY, 1D6N, 1HMP, 1Z7G, 2VFA, 3GEP, 3GGC, 3GGJ, 4IJQ, 4KN6
Identifiers
Symbols	HPRT1; HGPRT; HPRT
External IDs	OMIM: 308000 MGI: 96217 HomoloGene: 56590 ChEMBL: 2360 GeneCards: HPRT1 Gene
EC number	2.4.2.8
Gene Ontology
Molecular function	• nucleotide binding; • magnesium ion binding; • hypoxanthine phosphoribosyltransferase activity; • protein binding; • protein homodimerization activity; • guanine phosphoribosyltransferase activity;
Cellular component	• cytoplasm; • cytosol;
Biological process	• response to amphetamine; • purine nucleobase metabolic process; • purine nucleotide biosynthetic process; • purine ribonucleoside salvage; • adenine salvage; • guanine salvage; • behavior; • grooming behavior; • cytolysis; • striatum development; • cerebral cortex neuron differentiation; • central nervous system neuron development; • GMP salvage; • IMP salvage; • dopamine metabolic process; • purine-containing compound salvage; • hypoxanthine salvage; • small molecule metabolic process; • positive regulation of dopamine metabolic process; • GMP catabolic process; • IMP metabolic process; • hypoxanthine metabolic process; • lymphocyte proliferation; • dendrite morphogenesis; • protein homotetramerization; • nucleobase-containing small molecule metabolic process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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