{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:50:00Z","timestamp":1791561000463,"version":"4.3.4"},"reference-count":117,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioEssays"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The concept of \u2018metabolic structure\u2019, which considers metabolism as a stable, genetically encoded architecture with enzymes occupying fixed control positions, is indispensable but incomplete, and it obscures metabolism's true nature. I propose redefining metabolism as a dynamic field of emergent biochemical fluxes, governed by six fundamental parameters: time, water, entropy, quantum effects, space, and electrostatic potential, shaping the thermodynamic trajectories of living matter. Metabolic control analysis already supports this view: flux control coefficients are state\u2010 and time\u2010dependent coordinates within a thermodynamic field, not intrinsic enzyme properties. This perspective manifests across scales: electrostatics govern fructose 1,6\u2010bisphosphate cleavage in aldolase; hepatic zonation shows spatial reorganization through a single parameter; glucose deprivation quantitatively redirects intestinal cancer cell metabolism from glycolytic to oxidative flux, driving differentiation into an enterocyte\u2010like state; post\u2010meal walking redirects glucose flux from storage to oxidation without pharmacological intervention; inherited metabolic diseases can sometimes be managed without correcting the causal mutation. These examples converge into a new framework: metabolism possesses not only a sophisticated architecture but also states that shape its fluxes. And states, unlike static structures, can be reconfigured.<\/jats:p>","DOI":"10.1002\/bies.70193","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:03:06Z","timestamp":1791558186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Structure: A Paradigm Revisited in Light of the Fundamental Parameters of Living Systems"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8653-5521","authenticated-orcid":false,"given":"Jacques","family":"Fantini","sequence":"first","affiliation":[{"name":"Aix\u2010Marseille Universit\u00e9 (AMU) IHU M\u00e9diterran\u00e9e Infection Microbes Evolution Phylogeny and Infections (MEPHI)  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118657072"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(84)90214-7"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsfs.2023.0080"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/life14030280"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio-2016-0090"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.4c00555"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/icb\/icab167"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809838105"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0631607100"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1703781114"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biophys.35.040405.102134"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.6b00765"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cis.2014.05.002"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.ads4369"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201049404\u20109"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja902918p"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep26302"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1602916113"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr00023a011"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583500000615"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242216464"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom16010111"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/life16010118"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(00)01741-4"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12101527"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr800373w"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00305"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/v15020284"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2025.108797"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/v15091854"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar00145a005"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0480279"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja012205t"},{"key":"e_1_2_15_35_1","first-page":"65","article-title":"The Control of Flux","volume":"27","author":"Kacser H.","year":"1973","journal-title":"Symposia of the Society for Experimental Biology"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20101033.1974.tb03318.x"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0303\u20102647(75)90050\u20107"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2860313"},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biosystems.2023.105086"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20101033.1988.tb14128.x"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biosystems.2023.104984"},{"key":"e_1_2_15_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20105193(88)80073\u20100"},{"key":"e_1_2_15_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1990.tb19137.x"},{"key":"e_1_2_15_44_1","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/597913"},{"key":"e_1_2_15_45_1","doi-asserted-by":"publisher","DOI":"10.1006\/jtbi.1996.0167"},{"key":"e_1_2_15_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509831103"},{"key":"e_1_2_15_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)81026-8"},{"key":"e_1_2_15_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20101033.1974.tb03320.x"},{"key":"e_1_2_15_49_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432\u20101327.1999.00534.x"},{"key":"e_1_2_15_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2728(96)00026-6"},{"key":"e_1_2_15_51_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432\u20101327.1998.2580956.x"},{"key":"e_1_2_15_52_1","volume-title":"Self\u2010Organisation in Nonequilibrium Systems","author":"Nicolis G.","year":"1977"},{"key":"e_1_2_15_53_1","volume-title":"The Regulation of Cellular Systems","author":"Heinrich R.","year":"2012"},{"key":"e_1_2_15_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009234"},{"key":"e_1_2_15_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20101033.1980.tb04792.x"},{"key":"e_1_2_15_56_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1749933"},{"key":"e_1_2_15_57_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physchem.58.032806.104550"},{"key":"e_1_2_15_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/0301-4622(87)80072-8"},{"key":"e_1_2_15_59_1","doi-asserted-by":"publisher","DOI":"10.1187\/cbe.12-10-0170"},{"key":"e_1_2_15_60_1","doi-asserted-by":"publisher","DOI":"10.1187\/cbe.17-08-0169"},{"key":"e_1_2_15_61_1","volume-title":"The Vital Force: A Study of Bioenergetics","author":"Harold F. M.","year":"1987"},{"key":"e_1_2_15_62_1","doi-asserted-by":"publisher","DOI":"10.1021\/ed081p523"},{"key":"e_1_2_15_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr0503106"},{"key":"e_1_2_15_64_1","doi-asserted-by":"publisher","DOI":"10.1039\/c7sc01301a"},{"key":"e_1_2_15_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2021.06.006"},{"key":"e_1_2_15_66_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.5942"},{"key":"e_1_2_15_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1985.tb08876.x"},{"key":"e_1_2_15_68_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi700713s"},{"key":"e_1_2_15_69_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.8.2.291"},{"key":"e_1_2_15_70_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2SC01994A"},{"key":"e_1_2_15_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00138a018"},{"key":"e_1_2_15_72_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704968200"},{"key":"e_1_2_15_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi800049z"},{"key":"e_1_2_15_74_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi701350v"},{"key":"e_1_2_15_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.8b00919"},{"key":"e_1_2_15_76_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.0c02595"},{"key":"e_1_2_15_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(92)90055-5"},{"key":"e_1_2_15_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.01.012"},{"key":"e_1_2_15_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840020316"},{"key":"e_1_2_15_80_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1989.69.3.708"},{"key":"e_1_2_15_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510310201"},{"key":"e_1_2_15_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201049412\u20106"},{"key":"e_1_2_15_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010025\u201009616\u20105"},{"key":"e_1_2_15_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06611-5"},{"key":"e_1_2_15_85_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041220105"},{"key":"e_1_2_15_86_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.104.5.1199"},{"key":"e_1_2_15_87_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.83.1.235"},{"key":"e_1_2_15_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/0300\u20109084(89)90077\u20101"},{"key":"e_1_2_15_89_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1768-322X.1989.tb00785.x"},{"key":"e_1_2_15_90_1","first-page":"110","article-title":"Suramin\u2010treated HT29\u2010D4 Cells Grown in the Presence of Glucose in Permeable Culture Chambers Form Electrically Active Epithelial Monolayers. A Comparative Study With HT29\u2010D4 Cells Grown in the Absence of Glucose","volume":"51","author":"Fantini J.","year":"1990","journal-title":"European journal of cell biology"},{"key":"e_1_2_15_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)81797-5"},{"key":"e_1_2_15_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(92)90194-Z"},{"key":"e_1_2_15_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2009.01.013"},{"key":"e_1_2_15_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2020.110748"},{"key":"e_1_2_15_95_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0272449"},{"key":"e_1_2_15_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.06.036"},{"key":"e_1_2_15_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.131"},{"key":"e_1_2_15_98_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199909)180:3<431::AID-JCP14>3.0.CO;2-O"},{"key":"e_1_2_15_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2013.05.004"},{"key":"e_1_2_15_100_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.77.2.536"},{"key":"e_1_2_15_101_1","doi-asserted-by":"publisher","DOI":"10.18103\/mra.v2i7.368"},{"key":"e_1_2_15_102_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1226"},{"key":"e_1_2_15_103_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-020-02429-2"},{"key":"e_1_2_15_104_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0247211"},{"key":"e_1_2_15_105_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1335058"},{"key":"e_1_2_15_106_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13052\u2010024\u201001776\u2010w"},{"key":"e_1_2_15_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2020.101160"},{"key":"e_1_2_15_108_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/97.3-4.639"},{"key":"e_1_2_15_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2024.07.016"},{"key":"e_1_2_15_110_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00503.2020"},{"key":"e_1_2_15_111_1","doi-asserted-by":"publisher","DOI":"10.4172\/0974\u20108369.1000S3007"},{"key":"e_1_2_15_112_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00059"},{"key":"e_1_2_15_113_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3210707"},{"key":"e_1_2_15_114_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-07312-y"},{"key":"e_1_2_15_115_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20140226"},{"key":"e_1_2_15_116_1","doi-asserted-by":"publisher","DOI":"10.3184\/003685017X15063357842574"},{"key":"e_1_2_15_117_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajhb.21106"},{"key":"e_1_2_15_118_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.26.061505.111258"}],"container-title":["BioEssays"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bies.70193","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bies.70193","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bies.70193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:03:09Z","timestamp":1791558189000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bies.70193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":117,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/bies.70193"],"URL":"https:\/\/doi.org\/10.1002\/bies.70193","archive":["Portico"],"relation":{},"ISSN":["0265-9247","1521-1878"],"issn-type":[{"value":"0265-9247","type":"print"},{"value":"1521-1878","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70193"}}