Journal
REDOX BIOLOGY
Volume 43, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.redox.2021.101972
Keywords
Selenium-binding protein 1; Methanethiol oxidase; Caco-2 cells; Hydrogen sulfide; Hydrogen peroxide
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Funding
- Deutsche Forschungsgemeinschaft (DFG, Bonn, Germany) through Research Training Group ProMoAge [RTG 2155]
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Methanethiol is a gas produced by microbial degradation of methionine, primarily originating from bacteria in the human large intestine. SELENBP1 has been identified as a methanethiol oxidase, converting it to other substances. Using a novel assay, researchers confirmed the loss of MTO function in SELENBP1 variants and found that mature enterocytes are capable of eliminating microbiome-derived methanethiol.
Methanethiol, a gas with the characteristic smell of rotten cabbage, is a product of microbial methionine degradation. In the human body, methanethiol originates primarily from bacteria residing in the lumen of the large intestine. Selenium-binding protein 1 (SELENBP1), a marker protein of mature enterocytes, has recently been identified as a methanethiol oxidase (MTO). It catalyzes the conversion of methanethiol to hydrogen sulfide (H2S), hydrogen peroxide (H2O2) and formaldehyde. Here, human Caco-2 intestinal epithelial cells were subjected to enterocyte-like differentiation, followed by analysis of SELENBP1 levels and MTO activity. To that end, we established a novel coupled assay to assess MTO activity mimicking the proximity of microbiome and intestinal epithelial cells in vivo. The assay is based on in situ-generation of methanethiol as catalyzed by a bacterial recombinant L-methionine gamma-lyase (MGL), followed by detection of H2S and H2O2. Applying this assay, we verified the loss and impairment of MTO function in SELENBP1 variants (His329Tyr; Gly225Trp) previously identified in individuals with familial extraoral halitosis. MTO activity was strongly enhanced in Caco-2 cells upon enterocyte differentiation, in parallel with increased SELENBP1 levels. This suggests that mature enterocytes located at the tip of colonic crypts are capable of eliminating microbiome-derived methanethiol.
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