1. Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis
- Author
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Lambert P. van den Heuvel, G. Herma Renkema, Richard J. Rodenburg, Heike Olbrich, Heymut Omran, Huub J. M. Op den Camp, Marijn Oude Elberink, Ron A. Wevers, Christian Gilissen, Edwin Winkel, Albert Tangerman, K Otfried Schwab, Hanka Venselaar, J. Silvia Sequeira, Arjan Pol, Udo F. H. Engelke, Arjan P.M. de Brouwer, Kevin C K Lloyd, Jörn Oliver Sass, Renee S. Araiza, Hendrik Schäfer, and Personalized Healthcare Technology (PHT)
- Subjects
0301 basic medicine ,dimethylsulfide ,gasotransmitter ,Erythrocytes ,HDE MTB ,SELENIUM-BINDING PROTEIN-1 ,hydrogen sulfide ,GAS-CHROMATOGRAPHY ,Methanethiol ,Selenium-Binding Proteins ,Inbred C57BL ,medicine.disease_cause ,Inborn Error of Metabolism ,Mice ,chemistry.chemical_compound ,volatile organic compounds ,Hydrogen Sulfide ,Cells, Cultured ,chemistry.chemical_classification ,Mice, Knockout ,Mutation ,Cultured ,biology ,Glutathione peroxidase ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,3. Good health ,VOLATILE SULFUR-COMPOUNDS ,GLUTATHIONE-PEROXIDASE ,Biochemistry ,Breath Tests ,methanethiol oxidase ,Methanethiol Oxidase ,Methanethiol oxidase ,tumor suppessor ,Oxidoreductases ,methanethiol ,Dimethylsulfoxide ,Cells ,Knockout ,extra-oral halitosis ,BLOOD-BORNE HALITOSIS ,HYDROGEN-SULFIDE ,Article ,Cell Line ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,CEREBROSPINAL-FLUID ,Gasotransmitter ,Genetics ,medicine ,inborn error of metabolism ,cancer ,Animals ,Humans ,Dimethyl Sulfoxide ,Volatile Organic Compounds ,malodor ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,METHYL MERCAPTAN OXIDASE ,Extra-Oral Halitosis ,Halitosis ,biology.organism_classification ,medicine.disease ,dimethylsulfoxide ,QP ,QR ,Mice, Inbred C57BL ,030104 developmental biology ,Enzyme ,DIMETHYL SULFIDE ,Odor ,chemistry ,Inborn error of metabolism ,Ecological Microbiology ,erythrocytes ,HIGH-RESOLUTION H-1-NMR ,dimethylsulfone ,Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] ,Bacteria - Abstract
Selenium-binding protein 1 (SELENBP1) has been associated with several cancers, although its exact role is unknown. We show that SELENBP1 is a methanethiol oxidase (MTO), related to the MTO in methylotrophic bacteria, that converts methanethiol to H2O2, formaldehyde, and H2S, an activity not previously known to exist in humans. We identified mutations in SELENBP1 in five patients with cabbage-like breath odor. The malodor was attributable to high levels of methanethiol and dimethylsulfide, the main odorous compounds in their breath. Elevated urinary excretion of dimethylsulfoxide was associated with MTO deficiency. Patient fibroblasts had low SELENBP1 protein levels and were deficient in MTO enzymatic activity; these effects were reversed by lentivirus-mediated expression of wild-type SELENBP1. Selenbp1-knockout mice showed biochemical characteristics similar to those in humans. Our data reveal a potentially frequent inborn error of metabolism that results from MTO deficiency and leads to a malodor syndrome. info:eu-repo/semantics/publishedVersion
- Published
- 2018