Sandbox Reserved 1769: Difference between revisions

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=== Mechanism of Bile Salt Uptake ===

[[Image:ntcpmechanismoverall.png|350 px|right|thumb| Figure 4. Mechanism of bile salt uptake by NTCP. A bile salt and two Na+ ions bind to NTCP in the open-pore state. Transition to the inward-facing state allows release of the bile salt and ions into the cytoplasm.]]

NTCP utilizes secondary active transport to uptake bile salts from blood plasma into the cytoplasm of liver cells (Figure 4). The transport of one bile salt is driven by the downhill transport of 2 Na+ ions along sodium’s electrochemical gradient. Liu et al. proposes a mechanism in which two bile salts and two Na+ ions bind to the <scene name='95/952697/Ntcp_open-pore_state_surface/4'>open-pore state</scene> (Figure 4a), but only one bile salt (along with two Na+ ions) is released into the cytoplasm. After all substrates are bound, the conformational change from the open-pore state to the inward facing state is driven by the energetics of the favorable transport of Na+ ions. The <scene name='95/952697/Ntcp_inward_facing_state/3'>inward facing state</scene> (Figure 4b) allows release of one bile salt and two Na+ ions the cytoplasm. In this conformation, the pore closes off relative to the extracellular side and opens to the cytoplasmic side.<ref name="Asami" /> Afterwards, the remaining bile salt bound to NTCP shifts to the position the previous bile salt occupied, and the process repeats itself.<ref name = "Liu" /> [https://en.wikipedia.org/wiki/Active_transport#Secondary_active_transport Secondary active transport] The inherent amiphipathicity of bile acids allows passage through NTCP’s amphipathic pore (Figure 5)[[Image:Hydro_NEWEST_AdobeExpress_(1).gif|400 px|right|thumb|Figure 5. Amphipathic pore of NTCP highlighting hydrophobic residues (red) and hydrophilic residues (white).]].

NTCP utilizes secondary active transport to uptake bile salts from blood plasma into the cytoplasm of liver cells (Figure 4). The transport of one bile salt is driven by the downhill transport of 2 Na+ ions along sodium’s electrochemical gradient. Liu et al. proposes a mechanism in which two bile salts and two Na+ ions bind to the <scene name='95/952697/Ntcp_open-pore_state_surface/4'>open-pore state</scene> (Figure 4a), but only one bile salt (along with two Na+ ions) is released into the cytoplasm. After all substrates are bound, the conformational change from the open-pore state to the inward facing state is driven by the energetics of the favorable transport of Na+ ions. The <scene name='95/952697/Ntcp_inward_facing_state/3'>inward facing state</scene> (Figure 4b) allows release of one bile salt and two Na+ ions the cytoplasm. In this conformation, the pore closes off relative to the extracellular side and opens to the cytoplasmic side.<ref name="Asami" /> Afterwards, the remaining bile salt bound to NTCP shifts to the position the previous bile salt occupied, and the process repeats itself.<ref name = "Liu" /> [https://en.wikipedia.org/wiki/Active_transport#Secondary_active_transport Secondary active transport] The inherent amiphipathicity of bile acids allows passage through NTCP’s amphipathic pore (Figure 5)[[Image:Hydro_NEWEST_AdobeExpress_(1).gif|400 px|right|thumb|Figure 5. Amphipathic pore of NTCP highlighting hydrophobic residues (red) and hydrophilic residues (white). (PDB: [https://www.rcsb.org/structure/7PQQ 7PQQ]

=== Mechanism of HBV/HDV Infection ===

Sandbox Reserved 1769: Difference between revisions

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@@ Line 27: / Line 27: @@
 === Mechanism of Bile Salt Uptake ===
 [[Image:ntcpmechanismoverall.png|350 px|right|thumb| Figure 4. Mechanism of bile salt uptake by NTCP. A bile salt and two Na+ ions bind to NTCP in the open-pore state. Transition to the inward-facing state allows release of the bile salt and ions into the cytoplasm.]]
-NTCP utilizes secondary active transport to uptake bile salts from blood plasma into the cytoplasm of liver cells (Figure 4).  The transport of one bile salt is driven by the downhill transport of 2 Na+ ions along sodium’s electrochemical gradient.  Liu et al. proposes a mechanism in which two bile salts and two Na+ ions bind to the <scene name='95/952697/Ntcp_open-pore_state_surface/4'>open-pore state</scene> (Figure 4a), but only one bile salt (along with two Na+ ions) is released into the cytoplasm. After all substrates are bound, the conformational change from the open-pore state to the inward facing state is driven by the energetics of the favorable transport of Na+ ions.  The <scene name='95/952697/Ntcp_inward_facing_state/3'>inward facing state</scene> (Figure 4b) allows release of one bile salt and two Na+ ions the cytoplasm. In this conformation, the pore closes off relative to the extracellular side and opens to the cytoplasmic side.<ref name="Asami" /> Afterwards, the remaining bile salt bound to NTCP shifts to the position the previous bile salt occupied, and the process repeats itself.<ref name = "Liu" /> [https://en.wikipedia.org/wiki/Active_transport#Secondary_active_transport Secondary active transport] The inherent amiphipathicity of bile acids allows passage through NTCP’s amphipathic pore (Figure 5)[[Image:Hydro_NEWEST_AdobeExpress_(1).gif|400 px|right|thumb|Figure 5. Amphipathic pore of NTCP highlighting hydrophobic residues (red) and hydrophilic residues (white).]].
+NTCP utilizes secondary active transport to uptake bile salts from blood plasma into the cytoplasm of liver cells (Figure 4).  The transport of one bile salt is driven by the downhill transport of 2 Na+ ions along sodium’s electrochemical gradient.  Liu et al. proposes a mechanism in which two bile salts and two Na+ ions bind to the <scene name='95/952697/Ntcp_open-pore_state_surface/4'>open-pore state</scene> (Figure 4a), but only one bile salt (along with two Na+ ions) is released into the cytoplasm. After all substrates are bound, the conformational change from the open-pore state to the inward facing state is driven by the energetics of the favorable transport of Na+ ions.  The <scene name='95/952697/Ntcp_inward_facing_state/3'>inward facing state</scene> (Figure 4b) allows release of one bile salt and two Na+ ions the cytoplasm. In this conformation, the pore closes off relative to the extracellular side and opens to the cytoplasmic side.<ref name="Asami" /> Afterwards, the remaining bile salt bound to NTCP shifts to the position the previous bile salt occupied, and the process repeats itself.<ref name = "Liu" /> [https://en.wikipedia.org/wiki/Active_transport#Secondary_active_transport Secondary active transport] The inherent amiphipathicity of bile acids allows passage through NTCP’s amphipathic pore (Figure 5)[[Image:Hydro_NEWEST_AdobeExpress_(1).gif|400 px|right|thumb|Figure 5. Amphipathic pore of NTCP highlighting hydrophobic residues (red) and hydrophilic residues (white). (PDB: [https://www.rcsb.org/structure/7PQQ 7PQQ]
 === Mechanism of HBV/HDV Infection ===