Sandbox Reserved 1782: Difference between revisions

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== Background ==

[[Image:CARTOON.png|400 px|right|thumb|'''Figure 1.''' NTCP structure with both Na+ ions and bile salts bound with the NTCP molecule shown in light blue, the two Na+ ions shown in purple spheres, and the bile salts shown in sticks as dark blue. [PDB file 7ZYI].]]

*Sodium taurocholate co-transporting polypeptide (NTCP) is a sodium-dependent transporter ~~in the body~~ that is responsible for the transportation of bile salts from the blood into epithelial ~~liver cells. This carrier protein is responsible for a conformational change that allows bile salts to cross the cell membrane and enter the inside of~~ liver cells. <Ref> Goutam, K., Ielasi, F.S., Pardon, E. et al. Structural basis of sodium-dependent bile salt uptake into the liver. Nature 606, 1015–1020 (2022). [https://doi.org/10.1038/s41586-022-04723-z DOI: 10.1038/s41586-022-04723-z]. </Ref>~~. Both sodium ions and bile salts bind to~~ NTCP in the ~~same binding pocket on~~ the ~~molecule (Fig. 1). NTCP also acts as a receptor for Hepatitis B virus and Hepatitis D virus. The~~ bile salts transported by NTCP are located within the gastrointestinal tract of the body and play a very key role in many biological functions. These functions include digesting and absorbing nutrients by helping break down fats and transporting lipid soluble nutrients into the ~~liver. <Ref> Maldonado-Valderrama, J., Wilde, P., Macierzanka, A., & Mackie, A.~~ (~~2011). The role of bile salts in digestion~~. ~~Advances in colloid and interface science, 165(~~1), 36–46. [https://doi.org/10.1016/j.cis.2010.12.002 DOI: 10.1016/j.cis.2010.12.002]. </Ref>. The NTCP carrier protein itself can be found within hepatocytes, or the epithelial cells of the liver, but more specifically, within the basolateral membrane of these cells. <Ref name="Asami"> Asami J, Kimura KT, Fujita-Fujiharu Y, Ishida H, Zhang Z, Nomura Y, Liu K, Uemura T, Sato Y, Ono M, Yamamoto M, Noda T, Shigematsu H, Drew D, Iwata S, Shimizu T, Nomura N, Ohto U. Structure of the bile acid transporter and HBV receptor NTCP. Nature. 2022 Jun; 606 (7916):1021-1026. [https://dx.doi.org/10.1038/s41586-022-04845-4 DOI: 10.1038/s41586-022-04845-4]. </Ref>. The uptake of bile salts into the liver also allow for drugs to be both absorbed and excreted, as well as essential nutrients such as Vitamin A,D,E, and K to be absorbed in the small intestine.

*Sodium taurocholate co-transporting polypeptide (NTCP) is a sodium-dependent transporter that is responsible for the transportation of bile salts from the blood into epithelial liver cells. <Ref> Goutam, K., Ielasi, F.S., Pardon, E. et al. Structural basis of sodium-dependent bile salt uptake into the liver. Nature 606, 1015–1020 (2022). [https://doi.org/10.1038/s41586-022-04723-z DOI: 10.1038/s41586-022-04723-z]. </Ref> NTCP is a secondary active transport molecule that couples the thermodynamically favorable movement of Na+ ions with the unfavorable transport of bile salts into the cell (Fig. 1).

*The bile salts transported by NTCP in the gastrointestinal tract are involved in digestion, nutrient absorption, fat breakdown, and lipid soluble nutrient transport. <Ref> Maldonado-Valderrama, J., Wilde, P., Macierzanka, A., & Mackie, A. (2011). The role of bile salts in digestion. Advances in colloid and interface science, 165(1), 36–46. [https://doi.org/10.1016/j.cis.2010.12.002 DOI: 10.1016/j.cis.2010.12.002]. </Ref> NTCP is found within the basolateral membrane hepatocytes. <Ref name="Asami"> Asami J, Kimura KT, Fujita-Fujiharu Y, Ishida H, Zhang Z, Nomura Y, Liu K, Uemura T, Sato Y, Ono M, Yamamoto M, Noda T, Shigematsu H, Drew D, Iwata S, Shimizu T, Nomura N, Ohto U. Structure of the bile acid transporter and HBV receptor NTCP. Nature. 2022 Jun; 606 (7916):1021-1026. [https://dx.doi.org/10.1038/s41586-022-04845-4 DOI: 10.1038/s41586-022-04845-4]. </Ref> The uptake of bile salts into the liver also allow for drugs and fat soluble vitamins to be both absorbed and excreted in the small intestine. NTCP also acts as a receptor for Hepatitis B virus (HBV) and Hepatitis D virus (HDV).

=== Structural Overview ===

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 == Background ==
 [[Image:CARTOON.png|400 px|right|thumb|'''Figure 1.''' NTCP structure with both Na+ ions and bile salts bound with the NTCP molecule shown in light blue, the two Na+ ions shown in purple spheres, and the bile salts shown in sticks as dark blue. [PDB file 7ZYI].]]
-*Sodium taurocholate co-transporting polypeptide (NTCP) is a sodium-dependent transporter in the body that is responsible for the transportation of bile salts from the blood into epithelial liver cells. This carrier protein is responsible for a conformational change that allows bile salts to cross the cell membrane and enter the inside of liver cells. <Ref> Goutam, K., Ielasi, F.S., Pardon, E. et al. Structural basis of sodium-dependent bile salt uptake into the liver. Nature 606, 1015–1020 (2022). [https://doi.org/10.1038/s41586-022-04723-z DOI: 10.1038/s41586-022-04723-z]. </Ref>. Both sodium ions and bile salts bind to NTCP in the same binding pocket on the molecule (Fig. 1). NTCP also acts as a receptor for Hepatitis B virus and Hepatitis D virus. The bile salts transported by NTCP are located within the gastrointestinal tract of the body and play a very key role in many biological functions. These functions include digesting and absorbing nutrients by helping break down fats and transporting lipid soluble nutrients into the liver. <Ref> Maldonado-Valderrama, J., Wilde, P., Macierzanka, A., & Mackie, A. (2011). The role of bile salts in digestion. Advances in colloid and interface science, 165(1), 36–46. [https://doi.org/10.1016/j.cis.2010.12.002 DOI: 10.1016/j.cis.2010.12.002]. </Ref>. The NTCP carrier protein itself can be found within hepatocytes, or the epithelial cells of the liver, but more specifically, within the basolateral membrane of these cells. <Ref name="Asami"> Asami J, Kimura KT, Fujita-Fujiharu Y, Ishida H, Zhang Z, Nomura Y, Liu K, Uemura T, Sato Y, Ono M, Yamamoto M, Noda T, Shigematsu H, Drew D, Iwata S, Shimizu T, Nomura N, Ohto U. Structure of the bile acid transporter and HBV receptor NTCP. Nature. 2022 Jun; 606 (7916):1021-1026. [https://dx.doi.org/10.1038/s41586-022-04845-4 DOI: 10.1038/s41586-022-04845-4]. </Ref>. The uptake of bile salts into the liver also allow for drugs to be both absorbed and excreted, as well as essential nutrients such as Vitamin A,D,E, and K to be absorbed in the small intestine.
+*Sodium taurocholate co-transporting polypeptide (NTCP) is a sodium-dependent transporter that is responsible for the transportation of bile salts from the blood into epithelial liver cells. <Ref> Goutam, K., Ielasi, F.S., Pardon, E. et al. Structural basis of sodium-dependent bile salt uptake into the liver. Nature 606, 1015–1020 (2022). [https://doi.org/10.1038/s41586-022-04723-z DOI: 10.1038/s41586-022-04723-z]. </Ref> NTCP is a secondary active transport molecule that couples the thermodynamically favorable movement of Na+ ions with the unfavorable transport of bile salts into the cell (Fig. 1).
+*The bile salts transported by NTCP in the gastrointestinal tract are involved in digestion, nutrient absorption, fat breakdown, and lipid soluble nutrient transport. <Ref> Maldonado-Valderrama, J., Wilde, P., Macierzanka, A., & Mackie, A. (2011). The role of bile salts in digestion. Advances in colloid and interface science, 165(1), 36–46. [https://doi.org/10.1016/j.cis.2010.12.002 DOI: 10.1016/j.cis.2010.12.002]. </Ref> NTCP is found within the basolateral membrane hepatocytes. <Ref name="Asami"> Asami J, Kimura KT, Fujita-Fujiharu Y, Ishida H, Zhang Z, Nomura Y, Liu K, Uemura T, Sato Y, Ono M, Yamamoto M, Noda T, Shigematsu H, Drew D, Iwata S, Shimizu T, Nomura N, Ohto U. Structure of the bile acid transporter and HBV receptor NTCP. Nature. 2022 Jun; 606 (7916):1021-1026. [https://dx.doi.org/10.1038/s41586-022-04845-4 DOI: 10.1038/s41586-022-04845-4]. </Ref> The uptake of bile salts into the liver also allow for drugs and fat soluble vitamins to be both absorbed and excreted in the small intestine. NTCP also acts as a receptor for Hepatitis B virus (HBV) and Hepatitis D virus (HDV).
 === Structural Overview ===