Hepatic methanethiol oxidase (MTO) activity of mice requires adequate dietary supply of copper.

Selenium-binding protein 1 (SELENBP1) catalyzes the oxidative conversion of methanethiol to hydrogen sulfide, hydrogen peroxide and formaldehyde. Methanethiol oxidase (MTO) activity of recombinant human SELENBP1 was shown to require copper (Cu) ions, whereas selenium (Se) was largely dispensable. However, the impact of Cu and Se on MTO activity in mammals has not been explored so far. To investigate whether SELENBP1 levels and MTO activity in mice are affected by dietary availability of trace elements, liver samples of C57BL/6JRj mice held on diets deficient in Cu and/or Se for eight weeks were analyzed, as compared to mice fed the control diet with adequate trace element supply. Dietary Cu deficiency always resulted in diminished hepatic MTO activity, as detected by methanethiol-derived production of hydrogen sulfide. The effect of Cu deficiency was more pronounced in male than in female mice. Se deficiency only slightly, and solely in males, lowered MTO activity. Another sex-specific effect was observed with hepatic SELENBP1 levels: whereas diets deficient in Cu and/or Se increased SELENBP1 levels in males, they were decreased in female mice under Cu-deficient conditions. In addition to dietary Cu deficiency, MTO activity and SELENBP1 levels were explored in a rat model of Wilson's disease, which is characterized by hepatic Cu accumulation. Hepatic MTO activity was not altered in male and female rats under conditions of excess intrahepatic Cu, as long as the liver was not severely damaged. Notwithstanding the relatively low number of 5-6 animals included in each group, our data allow for the conclusion that hepatic MTO activity depends on adequate dietary Cu supply, whereas excess Cu does not further enhance the MTO activity of SELENBP1.