Unexpected roles for ADH1 and SORD in catalyzing the final step of erythritol biosynthesis
Autor: | Karsten Hiller, Martha S. Field, Doletha M. E. Szebenyi, Semira R Ortiz, Alexander Heinz, Lisa Schlicker |
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Přispěvatelé: | HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany. |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
L-Iditol 2-Dehydrogenase Sorbitol dehydrogenase glucose metabolism Dehydrogenase Erythritol Pentose phosphate pathway Biochemistry enzyme catalysis 03 medical and health sciences chemistry.chemical_compound Polyol enzyme kinetics Animals Humans Molecular Biology Alcohol dehydrogenase chemistry.chemical_classification 030102 biochemistry & molecular biology biology Alcohol Dehydrogenase Cell Biology 030104 developmental biology Enzyme Metabolism chemistry sorbitol dehydrogenase Liver A549 Cells Erythrose biology.protein biomarker alcohol dehydrogenase (ADH) Rabbits erythritol Tetroses |
Zdroj: | J Biol Chem The Journal of biological chemistry |
ISSN: | 1083-351X |
Popis: | The 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. |
Databáze: | OpenAIRE |
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