{"id":"https://openalex.org/W7213534096","doi":"https://doi.org/10.64898/2026.09.17.751990","title":"Threonine Supplementation Reduces Methylglyoxal Overflow by Increasing Glycolysis Flux at the Payoff Phase: A Metabolic Modeling Analysis","display_name":"Threonine Supplementation Reduces Methylglyoxal Overflow by Increasing Glycolysis Flux at the Payoff Phase: A Metabolic Modeling Analysis","publication_year":2026,"publication_date":"2026-09-18","ids":{"openalex":"https://openalex.org/W7213534096","doi":"https://doi.org/10.64898/2026.09.17.751990"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.17.751990","doi":"https://doi.org/10.64898/2026.09.17.751990","is_oa":false,"landing_page_url":"https://doi.org/10.64898/2026.09.17.751990","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5152103769","display_name":"Sandra Francis","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4405252405","display_name":"Srinivas University","ror":"https://ror.org/019qzkn95","country_code":"IN","type":"education","lineage":["https://openalex.org/I4405252405"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Sandra Francis","raw_affiliation_strings":["Central Research Laboratory, Srinivas University, Mukka, Mangalore, Karnataka, India"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Central Research Laboratory, Srinivas University, Mukka, Mangalore, Karnataka, India","institution_ids":["https://openalex.org/I4405252405"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5119944101","display_name":"Rahad Rehas","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4405252405","display_name":"Srinivas University","ror":"https://ror.org/019qzkn95","country_code":"IN","type":"education","lineage":["https://openalex.org/I4405252405"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Rahad Rehas","raw_affiliation_strings":["Central Research Laboratory, Srinivas University, Mukka, Mangalore, Karnataka, India"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Central Research Laboratory, Srinivas University, Mukka, Mangalore, Karnataka, India","institution_ids":["https://openalex.org/I4405252405"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5030675271","display_name":"Yuttamol Muangkram","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I135768898","display_name":"Ritsumeikan University","ror":"https://ror.org/0197nmd03","country_code":"JP","type":"education","lineage":["https://openalex.org/I135768898","https://openalex.org/I4390039241"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Yuttamol Muangkram","raw_affiliation_strings":["Research Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Research Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan","institution_ids":["https://openalex.org/I135768898"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101258688","display_name":"Niyas Rehman","orcid":"https://orcid.org/0009-0005-8015-365X","observed_orcids":["https://orcid.org/0009-0005-8015-365X"]},"institutions":[{"id":"https://openalex.org/I158688498","display_name":"Yenepoya University","ror":"https://ror.org/029zfa075","country_code":"IN","type":"education","lineage":["https://openalex.org/I158688498"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Niyas Rehman","raw_affiliation_strings":["Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, Karnataka, India"],"raw_orcid":"https://orcid.org/0009-0005-8015-365X","affiliations":[{"raw_affiliation_string":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, Karnataka, India","institution_ids":["https://openalex.org/I158688498"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023194441","display_name":"Anoop Kumar G. Velikkakath","orcid":"https://orcid.org/0000-0002-3863-918X","observed_orcids":["https://orcid.org/0000-0002-3863-918X"]},"institutions":[{"id":"https://openalex.org/I4405252405","display_name":"Srinivas University","ror":"https://ror.org/019qzkn95","country_code":"IN","type":"education","lineage":["https://openalex.org/I4405252405"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Anoop Kumar G Velikkakath","raw_affiliation_strings":["Central Research Laboratory, Srinivas University, Mukka, Mangalore, Karnataka, India"],"raw_orcid":"https://orcid.org/0000-0002-3863-918X","affiliations":[{"raw_affiliation_string":"Central Research Laboratory, Srinivas University, Mukka, Mangalore, Karnataka, India","institution_ids":["https://openalex.org/I4405252405"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034924637","display_name":"Shuhei Noda","orcid":"https://orcid.org/0000-0001-5430-1966","observed_orcids":["https://orcid.org/0000-0001-5430-1966"]},"institutions":[{"id":"https://openalex.org/I135768898","display_name":"Ritsumeikan University","ror":"https://ror.org/0197nmd03","country_code":"JP","type":"education","lineage":["https://openalex.org/I135768898","https://openalex.org/I4390039241"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Shuhei Noda","raw_affiliation_strings":["Research Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan"],"raw_orcid":"https://orcid.org/0000-0001-5430-1966","affiliations":[{"raw_affiliation_string":"Research Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan","institution_ids":["https://openalex.org/I135768898"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5037239790","display_name":"Michihiro Araki","orcid":"https://orcid.org/0000-0002-6686-4018","observed_orcids":["https://orcid.org/0000-0002-6686-4018"]},"institutions":[{"id":"https://openalex.org/I135768898","display_name":"Ritsumeikan University","ror":"https://ror.org/0197nmd03","country_code":"JP","type":"education","lineage":["https://openalex.org/I135768898","https://openalex.org/I4390039241"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Michihiro Araki","raw_affiliation_strings":["Graduate School of Pharmacy, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan"],"raw_orcid":"https://orcid.org/0000-0002-6686-4018","affiliations":[{"raw_affiliation_string":"Graduate School of Pharmacy, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan","institution_ids":["https://openalex.org/I135768898"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5037239790"],"corresponding_institution_ids":["https://openalex.org/I135768898"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10932","display_name":"Microbial Metabolic Engineering and Bioproduction","score":0.9907000064849854,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10932","display_name":"Microbial Metabolic Engineering and Bioproduction","score":0.9907000064849854,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11142","display_name":"Advanced Glycation End Products research","score":0.004600000102072954,"subfield":{"id":"https://openalex.org/subfields/1308","display_name":"Clinical Biochemistry"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12688","display_name":"Microbial metabolism and enzyme function","score":0.0020000000949949026,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/methylglyoxal","display_name":"methylglyoxal","score":0.9100000262260437},{"id":"https://openalex.org/keywords/threonine-supplementation","display_name":"threonine supplementation","score":0.9900000095367432},{"id":"https://openalex.org/keywords/advanced-glycation-end-products","display_name":"advanced glycation end products","score":0.847000002861023},{"id":"https://openalex.org/keywords/ethanol-production","display_name":"ethanol production","score":0.6510000228881836},{"id":"https://openalex.org/keywords/nad-regeneration","display_name":"NAD+ regeneration","score":0.8939999938011169},{"id":"https://openalex.org/keywords/acetaldehyde","display_name":"acetaldehyde","score":0.7630000114440918},{"id":"https://openalex.org/keywords/glyceraldehyde-3-phosphate","display_name":"glyceraldehyde-3-phosphate","score":0.9010000228881836},{"id":"https://openalex.org/keywords/glucose-metabolism","display_name":"glucose metabolism","score":0.5270000100135803},{"id":"https://openalex.org/keywords/escherichia-coli","display_name":"Escherichia coli","score":0.656000018119812},{"id":"https://openalex.org/keywords/metabolic-engineering","display_name":"metabolic engineering","score":0.492000013589859},{"id":"https://openalex.org/keywords/oxygen-limitation","display_name":"oxygen limitation","score":0.34299999475479126},{"id":"https://openalex.org/keywords/flux-balance-analysis","display_name":"flux balance analysis","score":0.48100000619888306}],"concepts":[{"id":"https://openalex.org/C2778592357","wikidata":"https://www.wikidata.org/wiki/Q903881","display_name":"Methylglyoxal","level":3,"score":0.8373000025749207},{"id":"https://openalex.org/C68709404","wikidata":"https://www.wikidata.org/wiki/Q1134475","display_name":"Flux (metallurgy)","level":2,"score":0.7250999808311462},{"id":"https://openalex.org/C167091322","wikidata":"https://www.wikidata.org/wiki/Q5463029","display_name":"Flux balance analysis","level":2,"score":0.7200000286102295},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7117999792098999},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.6837000250816345},{"id":"https://openalex.org/C20251656","wikidata":"https://www.wikidata.org/wiki/Q162643","display_name":"Glycolysis","level":3,"score":0.6802999973297119},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.5600000023841858},{"id":"https://openalex.org/C62231903","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Metabolism","level":2,"score":0.5076000094413757},{"id":"https://openalex.org/C2781135521","wikidata":"https://www.wikidata.org/wiki/Q8045523","display_name":"Xylose metabolism","level":4,"score":0.4690999984741211},{"id":"https://openalex.org/C6350086","wikidata":"https://www.wikidata.org/wiki/Q6822347","display_name":"Metabolic engineering","level":3,"score":0.44200000166893005},{"id":"https://openalex.org/C2775880066","wikidata":"https://www.wikidata.org/wiki/Q186521","display_name":"Threonine","level":4,"score":0.388700008392334},{"id":"https://openalex.org/C192989942","wikidata":"https://www.wikidata.org/wiki/Q68685","display_name":"Metabolic pathway","level":3,"score":0.375900000333786},{"id":"https://openalex.org/C2777866211","wikidata":"https://www.wikidata.org/wiki/Q5572349","display_name":"Glucose uptake","level":3,"score":0.37529999017715454},{"id":"https://openalex.org/C160941953","wikidata":"https://www.wikidata.org/wiki/Q6822342","display_name":"Metabolic flux analysis","level":3,"score":0.3610999882221222},{"id":"https://openalex.org/C17093226","wikidata":"https://www.wikidata.org/wiki/Q2734081","display_name":"Carbohydrate metabolism","level":2,"score":0.36059999465942383},{"id":"https://openalex.org/C101810790","wikidata":"https://www.wikidata.org/wiki/Q2263094","display_name":"Metabolic network","level":2,"score":0.35499998927116394},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.34860000014305115},{"id":"https://openalex.org/C2780282346","wikidata":"https://www.wikidata.org/wiki/Q24774081","display_name":"Glycerol kinase","level":3,"score":0.3206000030040741},{"id":"https://openalex.org/C147990577","wikidata":"https://www.wikidata.org/wiki/Q25790","display_name":"Glycation","level":3,"score":0.31769999861717224},{"id":"https://openalex.org/C2777595113","wikidata":"https://www.wikidata.org/wiki/Q61457","display_name":"Acetaldehyde","level":3,"score":0.3010999858379364},{"id":"https://openalex.org/C2779735320","wikidata":"https://www.wikidata.org/wiki/Q409618","display_name":"Dihydroxyacetone","level":3,"score":0.2874999940395355},{"id":"https://openalex.org/C2778839769","wikidata":"https://www.wikidata.org/wiki/Q12856814","display_name":"Sortase A","level":4,"score":0.28529998660087585},{"id":"https://openalex.org/C2780388412","wikidata":"https://www.wikidata.org/wiki/Q407569","display_name":"Gluconic acid","level":2,"score":0.2720000147819519},{"id":"https://openalex.org/C45656491","wikidata":"https://www.wikidata.org/wiki/Q1538418","display_name":"PEP group translocation","level":4,"score":0.2685000002384186},{"id":"https://openalex.org/C57600042","wikidata":"https://www.wikidata.org/wiki/Q227564","display_name":"Oxidative phosphorylation","level":2,"score":0.26840001344680786},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.26350000500679016},{"id":"https://openalex.org/C135870905","wikidata":"https://www.wikidata.org/wiki/Q903667","display_name":"Metabolome","level":3,"score":0.2599000036716461},{"id":"https://openalex.org/C2780881558","wikidata":"https://www.wikidata.org/wiki/Q132501","display_name":"Glycerol","level":2,"score":0.25929999351501465},{"id":"https://openalex.org/C20904676","wikidata":"https://www.wikidata.org/wiki/Q191835","display_name":"Gluconeogenesis","level":3,"score":0.2572999894618988},{"id":"https://openalex.org/C161573976","wikidata":"https://www.wikidata.org/wiki/Q420277","display_name":"Glucose transporter","level":3,"score":0.25450000166893005}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.17.751990","doi":"https://doi.org/10.64898/2026.09.17.751990","is_oa":false,"landing_page_url":"https://doi.org/10.64898/2026.09.17.751990","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":33,"referenced_works":["https://openalex.org/W1484553095","https://openalex.org/W2011514820","https://openalex.org/W2014490361","https://openalex.org/W2036676739","https://openalex.org/W2048465561","https://openalex.org/W2095203090","https://openalex.org/W2095407700","https://openalex.org/W2117760833","https://openalex.org/W2119642783","https://openalex.org/W2119960010","https://openalex.org/W2124737787","https://openalex.org/W2126333517","https://openalex.org/W2142073035","https://openalex.org/W2147032962","https://openalex.org/W2151937530","https://openalex.org/W2158119672","https://openalex.org/W2169377423","https://openalex.org/W2178215137","https://openalex.org/W2580985667","https://openalex.org/W2781635787","https://openalex.org/W2803682131","https://openalex.org/W2903148983","https://openalex.org/W2913553075","https://openalex.org/W2973932371","https://openalex.org/W3137111959","https://openalex.org/W3176251961","https://openalex.org/W3184933945","https://openalex.org/W4239203160","https://openalex.org/W4280529072","https://openalex.org/W4321612203","https://openalex.org/W4377987508","https://openalex.org/W4387904583","https://openalex.org/W4391322912"],"related_works":["https://openalex.org/W4301397374","https://openalex.org/W2803682131","https://openalex.org/W1809478430","https://openalex.org/W7206165081","https://openalex.org/W2345964440","https://openalex.org/W2093666125","https://openalex.org/W2398144389","https://openalex.org/W7097346045","https://openalex.org/W2041658170","https://openalex.org/W2092045636"],"abstract_inverted_index":{"Abstract":[0,246],"Methylglyoxal":[1],"(MGO)":[2],"is":[3],"a":[4,180],"metabolic":[5,33,63,89,219],"byproduct":[6],"of":[7,14,66,88,116,127,149],"sugar":[8],"metabolism":[9],"involved":[10],"in":[11,60,81,85,104,152,183,211,218,226],"the":[12,32,123,133,147,159,166,197],"formation":[13],"advanced":[15],"glycation":[16],"end":[17],"products":[18],"(AGEs)":[19],"and":[20,28,40,56,163,236],"its":[21],"accumulation":[22],"disrupts":[23],"protein":[24],"function,":[25],"redox":[26],"balance":[27,58],"cellular":[29],"viability.":[30],"Yet":[31],"rewiring":[34],"required":[35],"to":[36,78,110,135,138],"divert":[37],"MGO":[38,73,105,124,169,184,223],"overflow":[39,167],"prevent":[41],"these":[42,50,213,243],"cytotoxic":[43],"effects":[44],"remains":[45],"largely":[46],"unknown.":[47],"To":[48],"address":[49],"gaps,":[51],"we":[52],"used":[53],"flux":[54,57,74,106,137,148],"sampling":[55],"analysis":[59],"genome":[61],"scale":[62,84],"model":[64,205],"iJO1366":[65],"E.":[67],"coli":[68],".":[69],"High":[70],"glucose":[71,101,177],"increased":[72],"from":[75,107,242],"0.16":[76],"mmol/gDCW/h":[77,80,109],"1.87":[79,108],"simulation.":[82],"Large":[83],"silico":[86,114],"screening":[87],"reactions":[90],"identified":[91],"that":[92],"increasing":[93,97],"threonine":[94,191],"uptake,":[95],"thereby":[96,156],"ethanol":[98,117,136],"flux,":[99,185],"reduced":[100,173,189],"induced":[102],"increase":[103,182],"0.405":[111],"mmol/gDCW/h.":[112],"In":[113],"inhibition":[115],"production":[118],"(NAD":[119],"+":[120,142],"regeneration)":[121],"inhibited":[122],"lowering":[125],"potential":[126],"threonine.":[128],"Threonine":[129],"supplementation":[130],"actively":[131],"drives":[132],"acetaldehyde":[134],"provide":[139],"localized":[140],"NAD":[141],"relief,":[143],"which":[144,186],"subsequently":[145],"enhances":[146],"payoff":[150],"phase":[151],"glycolysis":[153],"(glyceraldehyde":[154],"3-phosphate),":[155],"efficiently":[157],"draining":[158],"stagnated":[160],"DHAP":[161],"pool":[162],"shutting":[164],"down":[165],"towards":[168],"production.":[170,224],"Unexpectedly,":[171],"under":[172],"oxygen":[174],"conditions,":[175],"high":[176],"caused":[178],"only":[179],"minimal":[181],"was":[187],"not":[188],"by":[190],"supplementation.":[192],"Our":[193],"study":[194],"also":[195],"decoded":[196],"mechanistic":[198],"details":[199],"behind":[200],"this":[201,204],"paradox.":[202],"Though":[203],"driven":[206],"hypothesis":[207],"requires":[208],"further":[209],"validation":[210],"vivo,":[212],"stoichiometric":[214],"predictions":[215],"have":[216],"applications":[217],"engineering,":[220],"for":[221],"commercial":[222],"Furthermore,":[225],"vivo":[227],"studies":[228],"focused":[229],"on":[230],"bacterial":[231],"stress,":[232],"gut":[233],"microbiome":[234],"imbalances":[235],"AGE":[237],"related":[238],"diseases":[239],"might":[240],"benefit":[241],"simulations.":[244],"Figure":[245]},"counts_by_year":[],"updated_date":"2026-10-28T10:33:24.094632","created_date":"2026-09-18T00:00:00"}
