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Mutat"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/j.1442-200X.1987.tb00037.x","article-title":"Developmental disorders in histidinemia\u2013follow-up study of language development in histidinemia","volume":"29","author":"M Ishikawa","year":"1987","journal-title":"Acta Paediatr Jpn"},{"key":"ref41","first-page":"127","article-title":"Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: the mechanism for reversible hypopigmentation in homocystinuria due to cystathionine beta-synthase deficiency","volume":"57","author":"O Reish","year":"1995","journal-title":"Am J Hum Genet"},{"key":"ref42","unstructured":"Phang JM, Chien-an AH, Valle D (2001) Disorders of proline and hydroxyproline metabolism.In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill."},{"key":"ref43","unstructured":"Chuang DT, Shih VE (2001) Maple syrup urine disease (branched-chain ketoaciduria).In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill."},{"key":"ref44","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1023\/A:1025121326959","article-title":"Maternal methionine adenosyltransferase I\/III deficiency: reproductive outcomes in a woman with four pregnancies","volume":"26","author":"SH Mudd","year":"2003","journal-title":"J Inherit Metab Dis"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/bies.950120706","article-title":"Perspectives on methylmalonic acidemia resulting from molecular cloning of methylmalonyl CoA mutase","volume":"12","author":"FD Ledley","year":"1990","journal-title":"Bioessays"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(10)60961-0","article-title":"Phenylketonuria","volume":"376","author":"N Blau","year":"2010","journal-title":"Lancet"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/(SICI)1098-1004(1998)12:4<267::AID-HUMU8>3.0.CO;2-C","article-title":"Dihydropteridine reductase deficiency: physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations","volume":"12","author":"I Dianzani","year":"1998","journal-title":"Hum Mutat"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/s00109-005-0648-2","article-title":"Tyrosinaemia type I - de novo mutation in liver tissue suppressing an inborn splicing defect","volume":"83","author":"YT Bliksrud","year":"2005","journal-title":"Journal of Molecular Medicine-Jmm"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1006\/mgme.2000.3085","article-title":"Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and Hawkinsinuria","volume":"71","author":"K Tomoeda","year":"2000","journal-title":"Molecular Genetics and Metabolism"},{"key":"ref50","unstructured":"Hamosh A, Johnston MV (2001) Nonketotic hyperglycinemia.In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill."},{"key":"ref51","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nbt.1614","article-title":"What is flux balance analysis?","volume":"28","author":"JD Orth","year":"2010","journal-title":"Nat Biotechnol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1039\/b914182k","article-title":"Integration of metabolomics and transcriptomics data to aid biomarker discovery in type 2 diabetes","volume":"6","author":"SC Connor","year":"2010","journal-title":"Mol Biosyst"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.cmet.2012.01.024","article-title":"Interplay between lipids and branched-chain amino acids in development of insulin resistance","volume":"15","author":"CB Newgard","year":"2012","journal-title":"Cell Metab"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nm1546","article-title":"Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment","volume":"13","author":"LR Brunham","year":"2007","journal-title":"Nat Med"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0009-8981(02)00427-8","article-title":"Altered glycosylation of alpha1-acid glycoprotein in patients with inflammation and diabetes mellitus","volume":"329","author":"K Higai","year":"2003","journal-title":"Clin Chim Acta"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"E1069","DOI":"10.1152\/ajpendo.00182.2007","article-title":"Analysis of N-glycan in serum glycoproteins from db\/db mice and humans with type 2 diabetes","volume":"293","author":"N Itoh","year":"2007","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.2337\/db06-1619","article-title":"Pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivity","volume":"56","author":"JM Aerts","year":"2007","journal-title":"Diabetes"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.2337\/db06-0719","article-title":"Inhibiting glycosphingolipid synthesis improves glycemic control and insulin sensitivity in animal models of type 2 diabetes","volume":"56","author":"H Zhao","year":"2007","journal-title":"Diabetes"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1007\/s00125-008-1014-z","article-title":"Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity","volume":"51","author":"M Skovbro","year":"2008","journal-title":"Diabetologia"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/1752-0509-6-153","article-title":"Reconstruction of genome-scale metabolic models for 126 human tissues using mCADRE","volume":"6","author":"Y Wang","year":"2012","journal-title":"BMC Syst 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of the adipocyte proteome by mass spectrometry and bioinformatics","volume":"6","author":"J Adachi","year":"2007","journal-title":"Mol Cell Proteomics"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1074\/mcp.M700304-MCP200","article-title":"Characterization of the human skeletal muscle proteome by one-dimensional gel electrophoresis and HPLC-ESI-MS\/MS","volume":"7","author":"K Hojlund","year":"2008","journal-title":"Mol Cell Proteomics"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.cell.2006.01.044","article-title":"Global survey of organ and organelle protein expression in mouse: combined proteomic and transcriptomic profiling","volume":"125","author":"T Kislinger","year":"2006","journal-title":"Cell"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/S0006-2952(02)01656-8","article-title":"Expression of acetoacetyl-CoA synthetase, a novel cytosolic ketone body-utilizing enzyme, in human brain","volume":"65","author":"M Ohgami","year":"2003","journal-title":"Biochem Pharmacol"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"26458","DOI":"10.1074\/jbc.M004160200","article-title":"Molecular characterization of human acetyl-CoA synthetase, an enzyme regulated by sterol regulatory element-binding proteins","volume":"275","author":"A Luong","year":"2000","journal-title":"J Biol Chem"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/0005-2760(71)90115-9","article-title":"The intracellular and intramitochondrial distribution of short-chain acyl-CoA synthetases in guinea-pig heart","volume":"231","author":"HR Scholte","year":"1971","journal-title":"Biochim Biophys Acta"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"11420","DOI":"10.1074\/jbc.M008782200","article-title":"Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the oxidation of acetate","volume":"276","author":"T Fujino","year":"2001","journal-title":"J Biol Chem"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/j.1939-165X.2005.tb00049.x","article-title":"Clinical biochemistry of pregnant and nursing mares","volume":"34","author":"JW Harvey","year":"2005","journal-title":"Vet Clin Pathol"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/S0369-8114(01)00232-2","article-title":"Research advances in ethanol metabolism","volume":"49","author":"VA Ramchandani","year":"2001","journal-title":"Pathol Biol (Paris)"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1080\/1042517021000011636","article-title":"Cloning and characterization of a novel human alcohol dehydrogenase gene (ADHFe1)","volume":"13","author":"Y Deng","year":"2002","journal-title":"DNA Seq"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/jbt.10057","article-title":"Human aldehyde dehydrogenases: potential pathological, pharmacological, and toxicological impact","volume":"17","author":"NE Sladek","year":"2003","journal-title":"J Biochem Mol Toxicol"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0378-1119(98)00181-4","article-title":"Isolation and characterization of an allelic cDNA for human muscle fructose-1,6-bisphosphatase","volume":"212","author":"H Tillmann","year":"1998","journal-title":"Gene"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"262","DOI":"10.2337\/diab.45.2.262","article-title":"Mitochondrial glycerol-3-phosphate dehydrogenase. Cloning of an alternatively spliced human islet-cell cDNA, tissue distribution, physical mapping, and identification of a polymorphic genetic marker","volume":"45","author":"J Ferrer","year":"1996","journal-title":"Diabetes"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/bies.1073","article-title":"Glycerol: a neglected variable in metabolic processes?","volume":"23","author":"D Brisson","year":"2001","journal-title":"Bioessays"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"531","DOI":"10.2337\/diabetes.48.3.531","article-title":"Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit-related protein","volume":"48","author":"SD Arden","year":"1999","journal-title":"Diabetes"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"6144","DOI":"10.1074\/jbc.273.11.6144","article-title":"Transmembrane topology of glucose-6-phosphatase","volume":"273","author":"CJ Pan","year":"1998","journal-title":"J Biol Chem"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"47098","DOI":"10.1074\/jbc.M309472200","article-title":"A glucose-6-phosphate hydrolase, widely expressed outside the liver, can explain age-dependent resolution of hypoglycemia in glycogen storage disease type Ia","volume":"278","author":"JJ Shieh","year":"2003","journal-title":"J Biol Chem"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"25197","DOI":"10.1074\/jbc.M101549200","article-title":"Cloning and characterization of the human and rat islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) genes","volume":"276","author":"CC Martin","year":"2001","journal-title":"J Biol Chem"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1677\/jme.0.0290205","article-title":"Identification and characterization of a human cDNA and gene encoding a ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein","volume":"29","author":"CC Martin","year":"2002","journal-title":"J Mol Endocrinol"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"21482","DOI":"10.1016\/S0021-9258(20)80563-8","article-title":"Isolation of the gene for murine glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1A","volume":"268","author":"LL Shelly","year":"1993","journal-title":"J Biol Chem"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"5311","DOI":"10.1073\/pnas.84.15.5311","article-title":"Epitopes of human testis-specific lactate dehydrogenase deduced from a cDNA sequence","volume":"84","author":"JL Millan","year":"1987","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0006-2952(01)00636-0","article-title":"Selective active site inhibitors of human lactate dehydrogenases A4, B4, and C4","volume":"62","author":"Y Yu","year":"2001","journal-title":"Biochem Pharmacol"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1042\/bj3150807","article-title":"Molecular cloning, sequencing and expression of the cDNA of the mitochondrial form of phosphoenolpyruvate carboxykinase from human liver","volume":"3)","author":"S Modaressi","year":"1996","journal-title":"Biochem J 315 (Pt"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1006\/bbrc.1994.1141","article-title":"Cloning of a complete protein-coding sequence of human platelet-type phosphofructokinase isozyme from pancreatic islet","volume":"198","author":"K Eto","year":"1994","journal-title":"Biochem Biophys Res Commun"},{"key":"ref95","unstructured":"Marks DB, Marks AD, Smith CM (1996) Basic medical biochemistry: a clinical approach. Baltimore: Williams &amp; Wilkins. xi, 806 p. p."},{"key":"ref96","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbrc.2004.05.205","article-title":"Hormonal regulation of lactate dehydrogenase-A through activation of protein kinase C pathways in MCF-7 breast cancer cells","volume":"320","author":"X Li","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"ref97","unstructured":"Champe PC, Harvey RA, Ferrier DR (2005) Biochemistry. Lippincott Williams &amp; Wilkins."},{"key":"ref98","unstructured":"Salway JG (1999) Metabolism at a glance. Oxford; Malden, MA: Blackwell Science."},{"key":"ref99","unstructured":"Nordlie RC, Sukalski KA (1985) The enzymes of biological membranes. Plenum Press."},{"key":"ref100","unstructured":"Orten JM, Neuhaus OW (1975) Human Biochemistry. C.V. Mosby &amp; Co."},{"key":"ref101","doi-asserted-by":"crossref","unstructured":"Devlin TM (2002) Textbook of Biochemistry with Clinical Correlations. John Wiley &amp; Sons, Inc., New York.","DOI":"10.1002\/0471254959"},{"key":"ref102","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-1-60761-232-2_6","article-title":"Human Protein Reference Database and Human Proteinpedia as discovery tools for systems biology","volume":"577","author":"TS Prasad","year":"2009","journal-title":"Methods Mol Biol"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"D411","DOI":"10.1093\/nar\/gkj141","article-title":"Human protein reference database\u20142006 update","volume":"34","author":"GR Mishra","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref104","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1101\/gr.1680803","article-title":"Development of human protein reference database as an initial platform for approaching systems biology in humans","volume":"13","author":"S Peri","year":"2003","journal-title":"Genome Res"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"D43","DOI":"10.1093\/nar\/gks1068","article-title":"Update on activities at the Universal Protein Resource (UniProt) in 2013","volume":"41","author":"R Apweiler","year":"2013","journal-title":"Nucleic Acids Research"},{"key":"ref106","doi-asserted-by":"crossref","first-page":"D764","DOI":"10.1093\/nar\/gks1049","article-title":"BRENDA in 2013: integrated reactions, kinetic data, enzyme function data, improved disease classification: new options and contents in BRENDA","volume":"41","author":"I Schomburg","year":"2013","journal-title":"Nucleic Acids Research"},{"key":"ref107","doi-asserted-by":"crossref","first-page":"D767","DOI":"10.1093\/nar\/gkn892","article-title":"Human Protein Reference Database-2009 update","volume":"37","author":"TSK Prasad","year":"2009","journal-title":"Nucleic Acids Research"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"D431","DOI":"10.1093\/nar\/gkh081","article-title":"BRENDA, the enzyme database: updates and major new developments","volume":"32","author":"I Schomburg","year":"2004","journal-title":"Nucleic Acids Research"},{"key":"ref109","doi-asserted-by":"crossref","first-page":"D115","DOI":"10.1093\/nar\/gkh131","article-title":"UniProt: the Universal Protein knowledgebase","volume":"32","author":"R Apweiler","year":"2004","journal-title":"Nucleic Acids Research"},{"key":"ref110","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/bioinformatics\/15.3.251","article-title":"METATOOL: for studying metabolic networks","volume":"15","author":"T Pfeiffer","year":"1999","journal-title":"Bioinformatics"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"D514","DOI":"10.1093\/nar\/gki033","article-title":"Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders","volume":"33","author":"A Hamosh","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"ref112","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ymben.2003.09.002","article-title":"The effects of alternate optimal solutions in constraint-based genome-scale metabolic models","volume":"5","author":"R Mahadevan","year":"2003","journal-title":"Metab Eng"},{"key":"ref113","doi-asserted-by":"crossref","first-page":"E1227","DOI":"10.1152\/ajpendo.00344.2005","article-title":"Effect of adipocyte beta3-adrenergic receptor activation on the type 2 diabetic MKR mice","volume":"290","author":"H Kim","year":"2006","journal-title":"Am J Physiol Endocrinol Metab"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0102319","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T07:17:26Z","timestamp":1649661446000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0102319"}},"subtitle":[],"editor":[{"given":"Thierry","family":"Alquier","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2014,7,16]]},"references-count":113,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2014,7,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0102319","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,16]]}}}