{"database":"BioModels","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Pdf":["https://www.ebi.ac.uk/biomodels/model/download/MODEL1012110001?filename=MODEL1012110001.pdf"],"Owl":["https://www.ebi.ac.uk/biomodels/model/download/MODEL1012110001?filename=MODEL1012110001-biopax2.owl","https://www.ebi.ac.uk/biomodels/model/download/MODEL1012110001?filename=MODEL1012110001-biopax3.owl"],"Svg":["https://www.ebi.ac.uk/biomodels/model/download/MODEL1012110001?filename=MODEL1012110001.svg"],"Xml":["https://www.ebi.ac.uk/biomodels/model/download/MODEL1012110001?filename=MODEL1012110001_url.xml","https://www.ebi.ac.uk/biomodels/model/download/MODEL1012110001?filename=MODEL1012110001_urn.xml"],"Other":["https://www.ebi.ac.uk/biomodels/model/download/MODEL1012110001?filename=MODEL1012110001.xpp","https://www.ebi.ac.uk/biomodels/model/download/MODEL1012110001?filename=MODEL1012110001.sci","https://www.ebi.ac.uk/biomodels/model/download/MODEL1012110001?filename=MODEL1012110001.png","https://www.ebi.ac.uk/biomodels/model/download/MODEL1012110001?filename=MODEL1012110001.m","https://www.ebi.ac.uk/biomodels/model/download/MODEL1012110001?filename=MODEL1012110001.vcml"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"submitter":["Nicolas Le Novère"],"curationStatus":["Non-curated"],"modellingApproach":["ordinary differential equation model"],"levelVersion":["L2V4"],"full_dataset_link":["https://www.ebi.ac.uk/biomodels/MODEL1012110001"],"publication_pubmed":["21114840"],"isPrivate":["false"],"repository":["BioModels"],"modelFormat":["SBML"],"omics_type":["Models"],"tokenised_name":["Li2010 YeastGlycolysis"],"publication_year":["2010"],"submissionId":["MODEL1012110001"],"publication_authors":["Peter Li, Joseph O Dada, Daniel Jameson, Irena Spasic, Neil Swainston, Kathleen Carroll, Warwick Dunn, Farid Khan, Naglis Malys, Hanan L Messiha, Evangelos Simeonidis, Dieter Weichart, Catherine Winder, Jill Wishart, David S Broomhead, Carole A Goble, Simon J Gaskell, D B Kell, Hans V Westerhoff, Pedro Mendes, Norman W Paton"],"first_author":["Peter Li"],"publication":["21114840,\n                            <h4>Background</h4>The behaviour of biological systems can be deduced from their mathematical models. However, multiple sources of data in diverse forms are required in the construction of a model in order to define its components and their biochemical reactions, and corresponding parameters. Automating the assembly and use of systems biology models is dependent upon data integration processes involving the interoperation of data and analytical resources.<h4>Results</h4>Taverna workflows have been developed for the automated assembly of quantitative parameterised metabolic networks in the Systems Biology Markup Language (SBML). A SBML model is built in a systematic fashion by the workflows which starts with the construction of a qualitative network using data from a MIRIAM-compliant genome-scale model of yeast metabolism. This is followed by parameterisation of the SBML model with experimental data from two repositories, the SABIO-RK enzyme kinetics database and a database of quantitative experimental results. The models are then calibrated and simulated in workflows that call out to COPASIWS, the web service interface to the COPASI software application for analysing biochemical networks. These systems biology workflows were evaluated for their ability to construct a parameterised model of yeast glycolysis.<h4>Conclusions</h4>Distributed information about metabolic reactions that have been described to MIRIAM standards enables the automated assembly of quantitative systems biology models of metabolic networks based on user-defined criteria. Such data integration processes can be implemented as Taverna workflows to provide a rapid overview of the components and their relationships within a biochemical system.. null, 11.\n                            School of Chemistry, The University of Manchester, Manchester M13 9PL, UK. peter.li@manchester.ac.uk"],"submitter_mail":["lenov@ebi.ac.uk"],"submitter_affiliation":["EBML-EBI"],"pubmed_abstract":["The PGM1 gene (also called GPM; Fraenkel 1982) coding for phosphoglyceromutase was isolated by functional complementation. When present on a multicopy vector and introduced into yeast cells it led to an about eightfold increase in specific enzymatic activity. This apparent overproduction was confirmed by SDS-polyacrylamide gel electrophoresis of crude extracts and at the transcriptional level by Northern analysis. By subcloning of the yeast DNA insertions of the plasmids originally isolated the PGM1 coding region was located within a 1.3 kb SalI-HindIII fragment. Integration at the chromosomal locus confirmed that the PGM1 gene had indeed been isolated. Southern analysis of genomic digests showed the same restriction patterns as the cloned sequences. However, a BamHI restriction polymorphism was observed. Furthermore, a repetitive element was found in the PGM1 flanking region. Finally, the chromosomal copy of the gene was deleted by replacement with a URA3 marker. The deletion mutants showed that the gene is not essential for yeast growing in the presence of a combination of glycerol and ethanol. However, growth was inhibited by glucose and neither glycerol nor ethanol alone were sufficient to support growth.","<h4>Background</h4>The behaviour of biological systems can be deduced from their mathematical models. However, multiple sources of data in diverse forms are required in the construction of a model in order to define its components and their biochemical reactions, and corresponding parameters. Automating the assembly and use of systems biology models is dependent upon data integration processes involving the interoperation of data and analytical resources.<h4>Results</h4>Taverna workflows have been developed for the automated assembly of quantitative parameterised metabolic networks in the Systems Biology Markup Language (SBML). A SBML model is built in a systematic fashion by the workflows which starts with the construction of a qualitative network using data from a MIRIAM-compliant genome-scale model of yeast metabolism. This is followed by parameterisation of the SBML model with experimental data from two repositories, the SABIO-RK enzyme kinetics database and a database of quantitative experimental results. The models are then calibrated and simulated in workflows that call out to COPASIWS, the web service interface to the COPASI software application for analysing biochemical networks. These systems biology workflows were evaluated for their ability to construct a parameterised model of yeast glycolysis.<h4>Conclusions</h4>Distributed information about metabolic reactions that have been described to MIRIAM standards enables the automated assembly of quantitative systems biology models of metabolic networks based on user-defined criteria. Such data integration processes can be implemented as Taverna workflows to provide a rapid overview of the components and their relationships within a biochemical system.","Hexokinase isoenzyme PI was cloned using a gene pool obtained from a yeast strain having only one functional hexokinase, isoenzyme PI. The gene was characterized using 20 restriction enzymes and located within a region of 2.0 kbp. The PI plasmid strongly hybridized with the PII plasmids isolated previously (Fröhlich et al. 1984). Hence there was a close relationship between the two genes, one of which must have been derived from the other by gene duplication. In contrast, glucose repression was restored only in hexokinase PII transformants; PI transformants remained non-repressible. This observation provided additional evidence for the hypothesis of Entian (1980) that only hexokinase PII is necessary for glucose repression. Furthermore, glucose phosphorylating activity in PI transformants exceeded that of wild-type cells, giving clear evidence that the phosphorylating capacity is not important for glucose repression.","Enolase (2-phospho-D-glycerate hydrolase, EC 4.2.1.11), particularly isoform neuron-specific enolase (NSE), is primarily localized in neurons and neuroendocrine cells and is a cancer diagnostic marker for brain tumors. Homology of enolase-coding DNA sequences from human, dog, cow, rat, mouse, rabbit, chicken, and yeast cells was investigated using hybridization techniques, percent sequence divergence, and amino acid analysis. Because enolase is a significant enzyme of the glycolytic pathway, enolase-coding DNA sequences have been found in all organisms tested so far. The human enzyme was found to be more like those of monkey and dog in structure than to those of chicken and yeast. The implications of the existence of the genetic conservation of enolase-coding DNA sequences in understanding concerted evolution as well as post-transcriptional regulation during differentiation are discussed. This is the first report is which sequence divergence in the coding region for enolase has been determined in a variety of organisms.","The Saccharomyces cerevisiae gene encoding the glycolytic enzyme pyruvate kinase has been isolated by complementation of a pyk mutant with DNA from a wild type yeast genomic library. Pyruvate kinase enzyme activity is 20-fold higher in the transformant compared to the parental strain and is glucose inducible. The cloned gene has been localized by hybridization of DNA fragments to yeast poly(A+) RNA and by complementation of the mutant defect with select subclones. A DNA sequence of 2885 nucleotides encoding a protein of 499 amino acids is reported. A polypeptide chain of 34 residues of the deduced yeast amino acid sequence closely resembles a peptide sequence at the ADP binding site of bovine muscle pyruvate kinase. The 5' end of the pyruvate kinase mRNA has been mapped and starts within the DNA sequence CAAG at -38 to -27 nucleotides upstream from the first ATG. We note that the sequence PyAAPu in this region appears to be a common consensus site for yeast RNA polymerase II transcriptional starts.","Yeast phosphofructokinase is an octamer composed of two different kinds of subunit. The genes coding for these subunits have been isolated by means of functional complementation in a pfk1 pfk2 double mutant. As a source of DNA the genomic library of Nasmyth and Tatchell (1980) constructed in the yeast multicopy vector YEp13 was used. Plasmids containing the information of one or the other gene were identified by back-transformation into pfk single mutants (pfk1 PFK2, PFK1 pfk2). Restriction maps of the respective insertions are provided. The genomic organization was confirmed by Southern analysis. Northern analysis showed hybridization to mRNAs of about 3.6 kb for both genes, corresponding to the molecular weight of the protein subunits. Transformation with one of the plasmids did not lead to an increase in phosphofructokinase activity. Subcloning of both genes in one multicopy vector (YEp13) and reintroduction into the yeast cell resulted in a 3.5-fold higher specific activity compared to the wild type. Overproduction of the protein subunits in this transformant was confirmed by SDS-polyacrylamide electrophoresis of crude extracts stained with Coomassie-blue. This was not accompanied by an increased ethanol production. The sequences encoding the two subunits were shown to share homology.","The complete amino acid sequence of yeast phosphoglycerate kinase, comprising 415 residues, was determined. The sequence of residues 1-173 was deduced mainly from nucleotide sequence analysis of a series of overlapping fragments derived from the relevant portion of a 2.95-kilobase endonuclease-HindIII-digest fragment containing the yeast phosphoglycerate kinase gene. The sequence of residues 174-415 was deduced mainly from amino acid sequence analysis of three CNBr-cleavage fragments, and from peptides derived from these fragments after digestion by a number of proteolytic enzymes. Cleavage at the two tryptophan residues with o-iodosobenzoic acid was also used to isolate fragments suitable for amino acid sequence analysis. Determination of the complete sequence now allows a detailed interpretation of the existing high-resolution X-ray-crystallographic structure. The sequence -Ile-Ile-Gly-Gly-Gly- occurs twice in distant parts of the linear sequence (residues 232-236 and 367-371). Both these regions contribute to the nucleoside phosphate-binding site. A comparison of the sequence of yeast phosphoglycerate kinase reported here with the sequences of phosphoglycerate kinase from horse muscle and human erythrocytes shows that the yeast enzyme is 64% identical with the mammalian enzymes. The yeast has strikingly fewer methionine, cysteine and tryptophan residues.","Two glycolytic enzymes, phosphoglucose isomerase and fructose-1,6-bisphosphate aldolase, of Saccharomyces cerevisiae could be replaced by their heterologous counterparts from Escherichia coli and Drosophila melanogaster. Both heterologous enzymes, which show respectively little and no sequence homology to the corresponding yeast enzymes, fully restored wild-type properties when their genes were expressed in yeast deletion mutants. This result does not support notions of an obligatory formation of glycolytic multi-enzyme aggregates in yeast; nor does it support possible regulatory functions of yeast phosphoglucose isomerase.","Utilizing yeast strains containing insertion mutations in each of the three glyceraldehyde-3-phosphate dehydrogenase structural genes, the level of expression of each gene was determined in logarithmically growing cells. The contribution of the TDH1, TDH2, and TDH3 gene products to the total glyceraldehyde-3-phosphate dehydrogenase activity in wild type cells is 10-15, 25-30, and 50-60%, respectively. The relative proportions of expression of each gene is the same in cells grown in the presence of glucose or ethanol as carbon source although the total glyceraldehyde-3-phosphate dehydrogenase activity in cells grown in the presence of glucose is 2-fold higher than in cells grown on ethanol. The polypeptides encoded by each of the structural genes were identified by two-dimensional polyacrylamide gel electrophoresis. The TDH3 structural gene encodes two resolvable forms of glyceraldehyde-3-phosphate dehydrogenase which differ by their net charge. The apparent specific activity of glyceraldehyde-3-phosphate dehydrogenase encoded by the TDH3 structural gene is severalfold lower than the enzymes encoded by TDH1 or TDH2. The polypeptides encoded by the TDH2 or TDH3 structural genes form catalytically active homotetramers. The apparent Vmax for the homotetramer encoded by TDH3 is 2-3-fold lower than the homotetramer encoded by TDH2. Evidence is presented that isozymes of glyceraldehyde-3-phosphate dehydrogenase exist in yeast cells, however, the number of different isozymes formed was not established. These data confirm that the three yeast glyceraldehyde-3-phosphate dehydrogenase genes encode catalytically active enzyme and that the genes are expressed at different levels during logarithmic cell growth."],"pubmed_title":["DNA sequences encoding enolase are remarkably conserved from yeast to mammals.","Isolation and characterization of the two structural genes coding for phosphofructokinase in yeast.","Isolation of the yeast phosphoglyceromutase gene and construction of deletion mutants.","Saccharomyces cerevisiae phosphoglucose isomerase and fructose bisphosphate aldolase can be replaced functionally by the corresponding enzymes of Escherichia coli and Drosophila melanogaster.","The isolation, characterization, and sequence of the pyruvate kinase gene of Saccharomyces cerevisiae.","Cloning of hexokinase isoenzyme PI from Saccharomyces cerevisiae: PI transformants confirm the unique role of hexokinase isoenzyme PII for glucose repression in yeasts.","Differential expression of the three yeast glyceraldehyde-3-phosphate dehydrogenase genes.","The complete amino acid sequence of yeast phosphoglycerate kinase.","Systematic integration of experimental data and models in systems biology."],"pubmed_authors":["Verma M M, Dutta S K SK","Perkins R E RE, Conroy S C SC, Dunbar B B, Fothergill L A LA, Tuite M F MF, Dobson M J MJ, Kingsman S M SM, Kingsman A J AJ","Boles E E, Zimmermann F K FK","Entian K D KD, Kopetzki E E, Fröhlich K U KU, Mecke D D","Heinisch J J","Rodicio R R, Heinisch J J","Li Peter P, Dada Joseph O JO, Jameson Daniel D, Spasic Irena I, Swainston Neil N, Carroll Kathleen K, Dunn Warwick W, Khan Farid F, Malys Naglis N, Messiha Hanan L HL, Simeonidis Evangelos E, Weichart Dieter D, Winder Catherine C, Wishart Jill J, Broomhead David S DS, Goble Carole A CA, Gaskell Simon J SJ, Kell Douglas B DB, Westerhoff Hans V HV, Mendes Pedro P, Paton Norman W NW","Burke R L RL, Tekamp-Olson P P, Najarian R R","McAlister L L, Holland M J MJ"],"additional_accession":[]},"is_claimable":false,"name":"Li2010_YeastGlycolysis","description":"\n      \n    This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.    \n        To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to    CC0 Public Domain Dedication\n        for more information.    \n      In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.\n        .    \n            \n        To cite BioModels Database, please use:    Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.\n            \n      \n    ","dates":{"last_modification":"2012-02-03","publication":"2005-01-01","submission":"2010-12-11"},"accession":"MODEL1012110001","cross_references":{"ec-code":["4.1.2.13","2.7.1.11","5.3.1.9","2.7.2.3","4.2.1.11","1.2.1.12","2.7.1.1","5.4.2.1","2.7.1.40","4.1.1.1"],"sgd":["S000001543","S000000400","S000000605","S000003486","S000003588","S000001949","S000001635","S000000036","S000004034"],"pubmed":["21114840","8435847","3007939","6347186","7520111","3905788","6394965","3033435","6185493"],"chebi":["CHEBI:16905","CHEBI:15422","CHEBI:15946","CHEBI:15954","CHEBI:16001","CHEBI:16761","CHEBI:17835","CHEBI:29052","CHEBI:15846","CHEBI:18367","CHEBI:17634","CHEBI:17794","CHEBI:15378","CHEBI:18021","CHEBI:15361","CHEBI:16108","CHEBI:15377","CHEBI:16908","CHEBI:15343","CHEBI:16526"],"biomodels__db":["MODEL1012110001"],"go":["GO:0005737","GO:0005886","GO:0005576"],"uniprot":["P14540","P16861","P16862","P12709","P00560","P00924","P00360","P04806","P00950","P00549","P06169"]}}