Estradiol, Estrone and Ethinyl Estradiol Metabolism Studied by High Resolution LC-MS/MS Using Stable Isotope Labeling and Trapping of Reactive Metabolites.

Biotransformation reactions that xenobiotics undergo during their metabolism are crucial for their proper excretion from the body, but can also be a source of toxicity, especially in the case of reactive metabolite formation. Unstable, reactive metabolites are capable of covalent binding to proteins, and have often been linked to liver damage and other undesired side effects. A common technique to assess the formation of reactive metabolites employs trapping them in vitro with glutathione and characterizing the resulting adducts by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).

Functional interaction of ubiquitin ligase RNF167 with UBE2D1 and UBE2N promotes ubiquitination of AMPA receptor.

Protein ubiquitination has been historically associated with protein degradation, but recent studies have demonstrated other cellular functions associated with substrate ubiquitination. Among the RING-type ubiquitin E3 ligase enzymes present in the human genome, RNF167 is a transmembrane protein located in endosomes and lysosomes and is implicated in controlling the endolysosomal pathway. Substrates of RNF167 have been identified, but the ubiquitin-conjugating E2 enzymes involved in the mechanism remain unknown.