5-ホスホリボシル1α-ニリン酸

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/01 18:29:57」(JST)

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Phosphoribosyl pyrophosphate (PRPP) is a pentosephosphate.

It is formed from ribose 5-phosphate by the enzyme ribose-phosphate diphosphokinase.

It plays a role in transferring phospho-ribose groups in several reactions:

Enzyme	Reactant	Product
adenine phosphoribosyltransferase	adenine	AMP
hypoxanthine-guanine phosphoribosyltransferase	guanine	GMP
hypoxanthine-guanine phosphoribosyltransferase	hypoxanthine	IMP
orotate phosphoribosyltransferase	orotate	OMP
uracil phosphoribosyltransferase	uracil	UMP

In de novo generation of purines, the enzyme amidophosphoribosyltransferase acts upon PRPP to create phosphoribosylamine.

Increased PRPP

Increased levels of PRPP is characterized by the overproduction and accumulation of uric acid leading to hyperuricemia and hyperuricosuria. It is one of the causes of gout.

Increased levels of PRPP are present in Lesch-Nyhan Syndrome. Decreased levels of hypoxanthine guanine phosphoribosyl transferase (HGPRT) causes this accumulation, as PRPP is a substrate used by HGPRT during purine salvage.

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1. 痛風再発の予防 prevention of recurrent gout

English Journal

Metabolic flux analysis of recombinant Pichia pastoris growing on different glycerol/methanol mixtures by iterative fitting of NMR-derived (13)C-labelling data from proteinogenic amino acids.

Jordà J, de Jesus SS, Peltier S, Ferrer P, Albiol J.Author information Departament d'Enginyeria Química, Escola d'Enginyeria, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain.AbstractThe yeast Pichia pastoris has emerged as one of the most promising yeast cell factories for the production of heterologous proteins. The readily available genetic tools and the ease of high-cell density cultivations using methanol or glycerol/methanol mixtures are among the key factors for this development. Previous studies have shown that the use of mixed feeds of glycerol and methanol seem to alleviate the metabolic burden derived from protein production, allowing for higher specific and volumetric process productivities. However, initial studies of glycerol/methanol co-metabolism in P. pastoris by classical metabolic flux analyses using (13)C-derived Metabolic Flux Ratio (METAFoR) constraints were hampered by the reduced labelling information obtained when using C3:C1 substrate mixtures in relation to the conventional C6 substrate, that is, glucose. In this study, carbon flux distributions through the central metabolic pathways in glycerol/methanol co-assimilation conditions have been further characterised using biosynthetically directed fractional (13)C labelling. In particular, metabolic flux distributions were obtained under 3 different glycerol/methanol ratios and growth rates by iterative fitting of NMR-derived (13)C-labelling data from proteinogenic amino acids using the software tool (13)CFlux2. Specifically, cells were grown aerobically in chemostat cultures fed with 80:20, 60:40 and 40:60 (w:w) glycerol/methanol mixtures at two dilutions rates (0.05hour(-1) and 0.16hour(-1)), allowing to obtain additional data (biomass composition and extracellular fluxes) to complement pre-existing datasets. The performed (13)C-MFA reveals a significant redistribution of carbon fluxes in the central carbon metabolism as a result of the shift in the dilution rate, while the ratio of carbon sources has a lower impact on carbon flux distribution in cells growing at the same dilution rate. At low growth rate, the percentage of methanol directly dissimilated to CO2 ranges between 50% and 70%. At high growth rate the methanol is completely dissimilated to CO2 by the direct pathway, in the two conditions of highest methanol content.
New biotechnology.N Biotechnol.2014 Jan 25;31(1):120-32. doi: 10.1016/j.nbt.2013.06.007. Epub 2013 Jul 8.
The yeast Pichia pastoris has emerged as one of the most promising yeast cell factories for the production of heterologous proteins. The readily available genetic tools and the ease of high-cell density cultivations using methanol or glycerol/methanol mixtures are among the key factors for this deve
PMID 23845285

De novo pyrimidine biosynthesis in the oomycete plant pathogen Phytophthora infestans.

Bayona LG1, Garavito MF1, Lozano GL2, Vasquez JJ1, Myers K3, Fry WE3, Bernal A4, Zimmermann BH2, Restrepo S5.Author information 1Laboratory of Mycology and Plant Pathology, Universidad de los Andes, Carrera 1 # 18-10, Edificio J-205, Bogotá DC, Colombia; Grupo de Investigaciones en Bioquímica y Biología Molecular de Parásitos, Universidad de los Andes, Carrera 1 # 18-10, Edificio M-301, Bogotá DC, Colombia.2Grupo de Investigaciones en Bioquímica y Biología Molecular de Parásitos, Universidad de los Andes, Carrera 1 # 18-10, Edificio M-301, Bogotá DC, Colombia.3Department of Plant Pathology and Plant-Microbe Biology, Cornell University, Ithaca, NY, USA.4Laboratory of Mycology and Plant Pathology, Universidad de los Andes, Carrera 1 # 18-10, Edificio J-205, Bogotá DC, Colombia.5Laboratory of Mycology and Plant Pathology, Universidad de los Andes, Carrera 1 # 18-10, Edificio J-205, Bogotá DC, Colombia. Electronic address: srestrep@uniandes.edu.co.AbstractThe oomycete Phytophthora infestans, causal agent of the tomato and potato late blight, generates important economic and environmental losses worldwide. As current control strategies are becoming less effective, there is a need for studies on oomycete metabolism to help identify promising and more effective targets for chemical control. The pyrimidine pathways are attractive metabolic targets to combat tumors, virus and parasitic diseases but have not yet been studied in Phytophthora. Pyrimidines are involved in several critical cellular processes and play structural, metabolic and regulatory functions. Here, we used genomic and transcriptomic information to survey the pyrimidine metabolism during the P. infestans life cycle. After assessing the putative gene machinery for pyrimidine salvage and de novo synthesis, we inferred genealogies for each enzymatic domain in the latter pathway, which displayed a mosaic origin. The last two enzymes of the pathway, orotate phosphoribosyltransferase and orotidine-5-monophosphate decarboxylase, are fused in a multi-domain enzyme and are duplicated in some P. infestans strains. Two splice variants of the third gene (dihydroorotase) were identified, one of them encoding a premature stop codon generating a non-functional truncated protein. Relative expression profiles of pyrimidine biosynthesis genes were evaluated by qRT-PCR during infection in Solanum phureja. The third and fifth genes involved in this pathway showed high up-regulation during biotrophic stages and down-regulation during necrotrophy, whereas the uracil phosphoribosyl transferase gene involved in pyrimidine salvage showed the inverse behavior. These findings suggest the importance of de novo pyrimidine biosynthesis during the fast replicative early infection stages and highlight the dynamics of the metabolism associated with the hemibiotrophic life style of pathogen.
Gene.Gene.2013 Dec 18. pii: S0378-1119(13)01670-3. doi: 10.1016/j.gene.2013.12.009. [Epub ahead of print]
The oomycete Phytophthora infestans, causal agent of the tomato and potato late blight, generates important economic and environmental losses worldwide. As current control strategies are becoming less effective, there is a need for studies on oomycete metabolism to help identify promising and more e
PMID 24361203

Understanding alternative fluxes/effluxes through comparative metabolic pathway analysis of phylum actinobacteria using a simplified approach.

Verma M, Lal D, Saxena A, Anand S, Kaur J, Kaur J, Lal R.Author information Molecular Biology Laboratory, Department of Zoology, University of Delhi, Delhi-110 007, India; Department of Zoology, Sri Venkateswara College, University of Delhi South Campus, New Delhi-110 021, India.AbstractActinobacteria are known for their diverse metabolism and physiology. Some are dreadful human pathogens whereas some constitute the natural flora for human gut. Therefore, the understanding of metabolic pathways is a key feature for targeting the pathogenic bacteria without disturbing the symbiotic ones. A big challenge faced today is multiple drug resistance by Mycobacterium and other pathogens that utilize alternative fluxes/effluxes. With the availability of genome sequence, it is now feasible to conduct the comparative in silico analysis. Here we present a simplified approach to compare metabolic pathways so that the species specific enzyme may be traced and engineered for future therapeutics. The analyses of four key carbohydrate metabolic pathways, i.e., glycolysis, pyruvate metabolism, tri carboxylic acid cycle and pentose phosphate pathway suggest the presence of alternative fluxes. It was found that the upper pathway of glycolysis was highly variable in the actinobacterial genomes whereas lower glycolytic pathway was highly conserved. Likewise, pentose phosphate pathway was well conserved in contradiction to TCA cycle, which was found to be incomplete in majority of actinobacteria. The clustering based on presence and absence of genes of these metabolic pathways clearly revealed that members of different genera shared identical pathways and, therefore, provided an easy method to identify the metabolic similarities/differences between pathogenic and symbiotic organisms. The analyses could identify isoenzymes and some key enzymes that were found to be missing in some pathogenic actinobacteria. The present work defines a simple approach to explore the effluxes in four metabolic pathways within the phylum actinobacteria. The analysis clearly reflects that actinobacteria exhibit diverse routes for metabolizing substrates. The pathway comparison can help in finding the enzymes that can be used as drug targets for pathogens without effecting symbiotic organisms within the same host. This may help to prevail over the multiple drug resistance, for designing broad spectrum drugs, in food industries and other clinical research areas.
Gene.Gene.2013 Dec 1;531(2):306-17. doi: 10.1016/j.gene.2013.08.076. Epub 2013 Sep 18.
Actinobacteria are known for their diverse metabolism and physiology. Some are dreadful human pathogens whereas some constitute the natural flora for human gut. Therefore, the understanding of metabolic pathways is a key feature for targeting the pathogenic bacteria without disturbing the symbiotic
PMID 24055419

Japanese Journal

先天性プリン代謝異常症による高尿酸血症 PRPP合成酵素亢進症 (特集高尿酸血症・痛風Update) -- (高尿酸血症診療の最新動向原発性高尿酸血症の病因・診断法研究の進歩)

飯笹泰蔵
日本臨床 66(4), 694-698, 2008-04
NAID 40015936525

Effect of Amplification of Desensitized purF and prs on Inosine Accumulation in Escherichia coli(MICROBIAL PHYSIOLOGY AND BIOTECHNOLOGY)

Shimaoka Megumi,Takenaka Yasuhiro,Kurahashi Osamu,Kawasaki Hisashi,Matsui Hiroshi
Journal of bioscience and bioengineering 103(3), 255-261, 2007-03-25
… The effect of a phosphoribosylpyrophosphate(PRPP) synthetase gene(prs) that was desensitized to feedback inhibition by ADP on inosine accumulation was investigated using an inosineproducing mutant of Escherichia coli. … At the same time, various types of plasmid having a PRPP amidotransferase gene(purF) that was desensitized to feedback inhibition by AMP and GMP were also investigated to improve inosine productivity using a compatible plasmid containing prs with a plasmid containing purF. …
NAID 110006271247

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★リンクテーブル★

リンク元	「高尿酸血症」「ヒポキサンチン・グアニンホスホリボシルトランスフェラーゼ」「5-ホスホリボシル1α-二リン酸」「アデニンホスホリボシルトランスフェラーゼ」
拡張検索	「PRPP合成酵素」「PRPPシンテターゼ」「PRPP synthetase」
関連記事	「PR」「PRP」

「高尿酸血症」

Phosphoribosyl pyrophosphate
Names
	Other names 5-phospho-alpha-D-ribose 1-diphosphate
Identifiers
CAS Number	7540-64-9
ChEBI	CHEBI:17111
ChemSpider	7062
DrugBank	DB01632
Jmol interactive 3D	Image
MeSH	Phosphoribosyl+pyrophosphate
PubChem	7339
	InChI InChI=1S/C5H13O14P3/c6-3-2(1-16-20(8,9)10)17-5(4(3)7)18-22(14,15)19-21(11,12)13/h2-7H,1H2,(H,14,15)(H2,8,9,10)(H2,11,12,13)/t2-,3-,4-,5-/m1/s1 Key: PQGCEDQWHSBAJP-TXICZTDVSA-N ; InChI=1/C5H13O14P3/c6-3-2(1-16-20(8,9)10)17-5(4(3)7)18-22(14,15)19-21(11,12)13/h2-7H,1H2,(H,14,15)(H2,8,9,10)(H2,11,12,13)/t2-,3-,4-,5-/m1/s1 Key: PQGCEDQWHSBAJP-TXICZTDVBW ;
	SMILES O=P(O[C@H]1O[C@@H]([C@@H](O)[C@H]1O)COP(=O)(O)O)(O)OP(=O)(O)O ;
Properties
Chemical formula	C5H13O14P3
Molar mass	390.07 g/mol
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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	Infobox references