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dc.contributor.authorSchlicker, Lisa
dc.contributor.authorSzebenyi, Doletha M E
dc.contributor.authorOrtiz, Semira R
dc.contributor.authorHeinz, Alexander
dc.contributor.authorHiller, Karsten
dc.contributor.authorField, Martha S
dc.date.accessioned2019-11-20T09:22:26Z
dc.date.available2019-11-20T09:22:26Z
dc.date.issued2019-11-01
dc.identifier.citationJ Biol Chem. 2019 Nov 1;294(44):16095-16108. doi: 10.1074/jbc.RA119.009049. Epub 2019 Sep 11.en_US
dc.identifier.issn1083-351X
dc.identifier.pmid31511322
dc.identifier.doi10.1074/jbc.RA119.009049
dc.identifier.urihttp://hdl.handle.net/10033/622020
dc.description.abstractThe low-calorie sweetener erythritol is endogenously produced from glucose through the pentose phosphate pathway in humans. Erythritol is of medical interest because elevated plasma levels of this polyol are predictive for visceral adiposity gain and development of type 2 diabetes. However, the mechanisms behind these associations remain unknown because the erythritol biosynthesis pathway, particularly the enzyme catalyzing the final step of erythritol synthesis (reduction of erythrose to erythritol), is not characterized. In this study, we purified two enzymes from rabbit liver capable of catalyzing the conversion of erythrose to erythritol: alcohol dehydrogenase 1 (ADH1) and sorbitol dehydrogenase (SORD). Both recombinant human ADH1 and SORD reduce erythrose to erythritol, using NADPH as a co-factor, and cell culture studies indicate that this activity is primarily NADPH-dependent. We found that ADH1 variants vary markedly in both their affinity for erythrose and their catalytic capacity (turnover number). Interestingly, the recombinant protein produced from the ADH1B2 variant, common in Asian populations, is not active when NADPH is used as a co-factor in vitro We also confirmed SORD contributes to intracellular erythritol production in human A549 lung cancer cells, where ADH1 is minimally expressed. In summary, human ADH1 and SORD catalyze the conversion of erythrose to erythritol, pointing to novel roles for two dehydrogenase proteins in human glucose metabolism that may contribute to individual responses to diet. Proteomics data are available via ProteomeXchange with identifier PXD015178.en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectalcohol dehydrogenase (ADH)en_US
dc.subjectbiomarkeren_US
dc.subjectenzyme catalysisen_US
dc.subjectenzyme kineticsen_US
dc.subjecterythritolen_US
dc.subjectglucose metabolismen_US
dc.subjectsorbitol dehydrogenaseen_US
dc.titleUnexpected roles for ADH1 and SORD in catalyzing the final step of erythritol biosynthesis.en_US
dc.typeArticleen_US
dc.contributor.departmentHIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.en_US
dc.identifier.journalJournal of Biological Chemistryen_US
dc.source.journaltitleThe Journal of biological chemistry


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