Sandbox Reserved 1769: Difference between revisions

To transport a single bile salt from the blood to the cytoplasm of the hepatocyte, <scene name='95/952697/Bothnabindingsites/4'>two sodium ions</scene> must bind to NTCP in the open-pore state, using two <scene name='95/952697/Bothnabindingsites/2'>sodium binding sites</scene>.<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>  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, as the transport of bile acids into the cell is thermodynamically unfavorable, but is coupled with the favorable transport of two sodium into into the cell to make the overall process thermodynamically favorable.<ref name = "Goutam" /> When the bile salts are released into the cell, NTCP transitions to the <scene name='95/952697/Ntcp_inward_facing_state/3'>inward facing state</scene>, where the pore is now closed to the extracellular side.