Metabolic production of methylated selenium species requires adequate methylation status

Abstract

Obesity negatively impacts methylation status and markers of methylation status vary according to selenium status in supplemented subjects. We have proposed that disruptions in methylation capacity induced by obesity compromise demonstrable anti‐cancer effects of Se supplementation. In order to address this hypothesis, we performed studies to determine if a systemic disruption in methylation capacity alters the distribution of methylated Se species. We intraperitoneal injected rats with selenite alone or in combination with an inhibitor of adenosylhomocysteine hydrolase (POA), and analyzed markers of methylation capacity as well as methylated Se species in various tissues. Results show that POA treatment disrupted S‐adenosylmethione (SAM):S‐adenosylhomocysteine (SAH) ratios in liver and kidney without significantly affecting homocysteine, folate or vitamin B12 concentrations. That treatment also altered, to varying degrees, the distributions of trimethylselenonium ion, a galactopyranoside selenosugar, Se‐methylselenocysteine and selenomethionine in liver, kidney and urine, demonstrating that disrupted methylation capacity affects Se metabolism. That this phenomenon may affect Se‐antitumorigenicity is suggested by the fact that these methylated Se species are metabolically related to methylselenol, which has been shown to have anti‐carcinogenic activity.