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Mechanistic Aspects of Selenium Delivery by Selenoprotein P

Selenoprotein P (SELENOP) is a serum glycoprotein that is required for proper selenium distribution in mammals, particularly in supplying selenium to the brain and testes. As the sole mechanism for providing essential selenium to developing spermatazoa, SELENOP metabolism is central to male fertility in all mammals. In addition, this process is important for proper brain function, especially under conditions of limited dietary selenium. Several specific and nonspecific mechanisms for SELENOP uptake in target tissues have been described but the utilization of the protein as a source of selenium for intracellular selenoprotein production has not been systematically characterized. We have examined the process by which SELENOP delivers selenium to cells using a robust selenium uptake assay that measures selenium utilization in cells fed 75Se‐radiolabeled SELENOP. Using a series of inhibitors and modulators we have identified specific requirements and regulators of the process.