Sandbox Reserved 1769: Difference between revisions
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=== Mechanism of Bile Salt Uptake === | === Mechanism of Bile Salt Uptake === | ||
[[Image:ntcpmechanismoverall.png| | [[Image:ntcpmechanismoverall.png|350 px|right|thumb| Figure 4. Mechanism of bile salt uptake by NTCP.]] | ||
NTCP utilizes secondary active transport to uptake bile salts from blood into the cytoplasm of liver cells (Figure 4). NTCP is crucial for bile salt homeostasis. Specific substrate binding pockets for bile salts have not been identified on NTCP, so the exact mechanism of uptake is unknown. However, it is known that bile salts recognize and bind to the <scene name='95/952697/Ntcp_open-pore_state_surface/4'>open-pore state</scene> (Figure 4a), characterized by an exposed region on the extracellular side. After binding, bile salts pass through the amphipathic pore [[Image:Hydro_NEWEST_AdobeExpress_(1).gif|400 px|left|thumb|Figure 5. Amphipathic pore of NTCP highlighting hydrophobic residues (red) and hydrophilic residues (white).]](Figure 5), and NTCP transitions into the <scene name='95/952697/Ntcp_inward_facing_state/3'>inward facing state</scene> (Figure 4b). In this conformation, the pore closes off relative to the extracellular side and opens to the cytoplasmic side. Transition to the inward facing state allows release of bile salts and sodium ions. It is not yet known how this transition exactly proceeds.<ref name="Asami" /> | NTCP utilizes secondary active transport to uptake bile salts from blood into the cytoplasm of liver cells (Figure 4). NTCP is crucial for bile salt homeostasis. Specific substrate binding pockets for bile salts have not been identified on NTCP, so the exact mechanism of uptake is unknown. However, it is known that bile salts recognize and bind to the <scene name='95/952697/Ntcp_open-pore_state_surface/4'>open-pore state</scene> (Figure 4a), characterized by an exposed region on the extracellular side. After binding, bile salts pass through the amphipathic pore [[Image:Hydro_NEWEST_AdobeExpress_(1).gif|400 px|left|thumb|Figure 5. Amphipathic pore of NTCP highlighting hydrophobic residues (red) and hydrophilic residues (white).]](Figure 5), and NTCP transitions into the <scene name='95/952697/Ntcp_inward_facing_state/3'>inward facing state</scene> (Figure 4b). In this conformation, the pore closes off relative to the extracellular side and opens to the cytoplasmic side. Transition to the inward facing state allows release of bile salts and sodium ions. It is not yet known how this transition exactly proceeds.<ref name="Asami" /> | ||