Abstract
Selenium is a nonmetal trace element that is critical for several redox reactions and utilized to produce the amino acid selenocysteine (Sec), which can be incorporated into selenoproteins. Selenocysteine lyase (SCL) is an enzyme which decomposes Sec into selenide and alanine, releasing the selenide to be further utilized to synthesize new selenoproteins. Disruption of the selenocysteine lyase gene (Scly) in mice (Scly−/− or Scly KO) led to obesity with dyslipidemia, hyperinsulinemia, glucose intolerance and lipid accumulation in the hepatocytes. As the liver is a central regulator of glucose and lipid homeostasis, as well as selenium metabolism, we aimed to pinpoint hepatic molecular pathways affected by the Scly gene disruption. Using RNA sequencing and metabolomics, we identified differentially expressed genes and metabolites in the livers of Scly KO mice. Integrated omics revealed that biological pathways related to amino acid metabolism, particularly alanine and glycine metabolism, were affected in the liver by disruption of Scly in mice with selenium adequacy. We further confirmed that hepatic glycine levels are elevated in male, but not in female, Scly KO mice. In conclusion, our results reveal that Scly participates in the modulation of hepatic amino acid metabolic pathways.
Highlights
The trace element selenium is classically known for being critical to enhancing the efficiency of several redox reactions, attributed to the presence of the selenium-containing amino acid selenocysteine (Sec), an integral part of a group of proteins called selenoproteins [1]
Mice (Figure 1 and Supplementary Table S3), with most of the changes being accentuated by selenium deficiency in the selenocysteine lyase gene (Scly) KO mice
Full RNA Sequencing (RNA-Seq) results can be found on the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository under Accession
Summary
The trace element selenium is classically known for being critical to enhancing the efficiency of several redox reactions, attributed to the presence of the selenium-containing amino acid selenocysteine (Sec), an integral part of a group of proteins called selenoproteins [1]. Sec decomposition is catalyzed by the enzyme, selenocysteine lyase Data Bank; EC:4.4.1.16; mSCL for the murine SCL), resulting in the release of selenide and alanine [3]. Selenide is postulated to be delivered back to selenoprotein synthesis [4]. Gene expression and mSCL expression and activity are highest in the kidneys and liver. The liver, in particular, is a major storage site for selenium and the site where selenium metabolism is coordinated in vertebrates
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