Sandbox Reserved 1769: Difference between revisions

To transport a single bile salt from the blood to the cytoplasm of the hepatocyte, two sodium ions are required to be bound to to NTCP in the open-pore state.<Ref name="Liu"> Liu H, Irobalieva RN, Bang-Sørensen R, Nosol K, Mukherjee S, Agrawal P, Stieger B, Kossiakoff AA, Locher KP. Structure of human NTCP reveals the basis of recognition and sodium-driven transport of bile salts into the liver. Cell Res. 2022 Aug;32(8):773-776. [https://dx.doi.org/10.1038/s41422-022-00680-4 DOI: 10.1038/s41422-022-00680-4]. </Ref> Thus, there are two <scene name='95/952697/Ntcp_complex_sodiumsites/10'>sodium binding sites</scene>. The residues in the <scene name='95/952697/Ntcp_complex_sodiumsites/14'>first sodium binding site</scene> include S105, N106, T123, and E257. The residues in the <scene name='95/952697/Ntcp_complex_sodiumsites/13'>second sodium binding site</scene> include Q68 and Q261. Mutations to these significant residues inhibit the binding of sodium ions, and consequently, inhibit the transport of bile salts by NTCP.<ref name = "Liu" /> [https://en.wikipedia.org/wiki/Active_transport#Secondary_active_transport Secondary active transport] is used here, as the transport of bile acids into the cell is so thermodynamically unfavorable that the reaction has to be coupled to the favorable transport of two sodium into into the cell.<ref name = "Goutam" /> When the bile salts are released into the cell, the protein is then found in the inward facing conformation, in which the pore through which the it had just passed is now closed to the extracellular side.