User:Matthew J Lowry/Sandbox 1

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This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
== Mechanism ==
== Mechanism ==
-
Montelukast is a leukotriene receptor antagonist that uses a very specific dual mechanism of action where it acts as both a bronchodilator and an anti-inflammatory<ref name=“fifteen”>Diamant, Z., Mantzouranis, E., & Bjermer, L. (2009). Montelukast in the treatment of asthma and beyond. Expert Reviews, 5, 639-658. doi:10.1586/eci.09.62</ref>.
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Montelukast is a leukotriene receptor antagonist that uses a very specific dual mechanism of action where it acts as both a bronchodilator and an anti-inflammatory<ref name=“fifteen”>Diamant, Z., Mantzouranis, E., & Bjermer, L. (2009). Montelukast in the treatment of asthma and beyond. Expert Reviews, 5, 639-658. doi:10.1586/eci.09.62</ref>.It accomplishes this by preventing the binding of receptors to a receptor site involved in the 5-lipoxygenase pathway, or more commonly known as the leukotriene cascade. Leukotrienes are better known for their role in producing inflammation, hyper responsiveness, bronchoconstriction, and increased smooth muscle contraction of the airways; they are able to produce these effects by binding to the cysteinyl leukotriene 1 receptor (CysLT1) . <ref name=”sixteen”>Nayak, A. (2004). A review of montelukast in the treatment of asthma and allergic rhinitis. Expert Opinion on Pharmacotherapy, 5:3, 679-686. doi:10.1517/14656566.5.3.679</ref>.
 +
 +
All leukotrienes involved in the 5-lipoxygenase pathway are synthesized from the fatty acid arachidonic acid<ref name=”seventeen”>Drazen, J., Elliot, I., & O’Byrne, P. (1999). Treatment of Asthma with Drugs Modifying the Leukotriene Pathway. The New England Journal of Medicine, 340, 197-206. doi:10.1056/NEJM199901213400306</ref>.; this acid is converted into the intermediate 5-hydroperoxyeicosatetraenioc acid (5-HPETE) by 5-lipoxygenase, and then 5-lipoxygenase quickly converts this into leukotriene A4 (LTA4) <ref name=”eighteen”>Wenzel, S.E. (1997). Arachidonic Acid Metabolites: Mediators of Inflammation in Asthma. Pharmacotherapy, 17, 3S-12S. doi:10.1002/j.1875-9114.1997tbo3696.x</ref>.LTA4 is a very unstable leukotriene and quickly follows one of two pathways: either its epoxide hydrolase catalyzes the conversion of LTA4 into LTB4, or LTC4 synthase converts it into LTC4 <ref name=”eighteen”>Wenzel, S.E. (1997). Arachidonic Acid Metabolites: Mediators of Inflammation in Asthma. Pharmacotherapy, 17, 3S-12S. doi:10.1002/j.1875-9114.1997tbo3696.x</ref>. Each of these leukotrienes precedes their own pathway with LTC4 continuing the cascade to produce subsequent leukotrienes D4 and E4.
 +
 +
Once synthesized in the cytosol of cells within lung tissue, LTC4 is carried by a transmembrane transporter to the extracellular space where it initiates the production of LTD4 and LTE4; leukotrienes C4 and D4 have equal ability to stimulate smooth muscle constriction in the airway, while E4 is not as strong of a muscle constrictor <ref name=”seventeen”>Drazen, J., Elliot, I., & O’Byrne, P. (1999). Treatment of Asthma with Drugs Modifying the Leukotriene Pathway. The New England Journal of Medicine, 340, 197-206. doi:10.1056/NEJM199901213400306</ref>. Each of these leukotrienes can bind to a CysLT receptor producing symptoms associated with asthma and also leading to increased edema formation, mucus secretion, and a decrease in mucus clearance <ref name=”eighteen”>Wenzel, S.E. (1997). Arachidonic Acid Metabolites: Mediators of Inflammation in Asthma. Pharmacotherapy, 17, 3S-12S. doi:10.1002/j.1875-9114.1997tbo3696.x</ref>. Montelukast acts as an antagonist by blocking the leukotrienes from binding at the CysLT receptor therefore, preventing the previously discussed symptoms from occurring; it is easy to think of Montelukast as a key that fits into a lock, but does not turn it.
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Less information is known about the specifics of how Montelukast may affect the LTB4 pathway; once LTB4 is synthesized from arachidonic acid it is also carried to the extracellular space by a transmembrane transporter; once in the extracellular space it binds to the B leukotriene receptor, known as BLT <ref name=”seventeen”>Drazen, J., Elliot, I., & O’Byrne, P. (1999). Treatment of Asthma with Drugs Modifying the Leukotriene Pathway. The New England Journal of Medicine, 340, 197-206. doi:10.1056/NEJM199901213400306</ref>.This leukotriene is a strong neutrophil-chemo-attracting compound that can cause neutrophilic adhesion, mucus generation, and can aid in increasing inflammation seen during asthma <ref name=”eighteen”>Wenzel, S.E. (1997). Arachidonic Acid Metabolites: Mediators of Inflammation in Asthma. Pharmacotherapy, 17, 3S-12S. doi:10.1002/j.1875-9114.1997tbo3696.x</ref>.It is hypothesized that Montelukast may inhibit 5-lipooxygenase in neutrophils, monocytes, and macrophages possibly preventing the production of LTB4 <ref name=”nineteen”>Tintinger, G., Feldman, C., Theron, A., and Anderson, R. (2010) Montelukast:more than a cysteinyl leukotriene receptor antagonist? The Scientific World Journal, 10, 2403-2413. doi:10.1100/tsw.2010.229.</ref>.This mechanism for Montelukast would also be distinct from the mechanism used in the cascade involving leukotriene’s C4, D4, and E4. It is also thought that the amount of Montelukast needed to prevent production of LTB4 would need to be greater than that needed to prevent the CysLT cascade <ref name=”nineteen”>Tintinger, G., Feldman, C., Theron, A., and Anderson, R. (2010) Montelukast:more than a cysteinyl leukotriene receptor antagonist? The Scientific World Journal, 10, 2403-2413. doi:10.1100/tsw.2010.229.</ref>.
</StructureSection>
</StructureSection>
== References ==
== References ==
<references/>
<references/>

Revision as of 00:35, 14 November 2016

This is a default text for your page Matthew J Lowry/Sandbox 1. Click above on edit this page to modify. Be careful with the < and > signs. You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue.

Contents

Function

Disease

Relevance

Structural highlights

Insert caption here

Drag the structure with the mouse to rotate

Montelukast has the chemical formula of C35H36ClNO3S with a molecular weight of 586.187 Da [3].

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

Mechanism

Montelukast is a leukotriene receptor antagonist that uses a very specific dual mechanism of action where it acts as both a bronchodilator and an anti-inflammatory[4].It accomplishes this by preventing the binding of receptors to a receptor site involved in the 5-lipoxygenase pathway, or more commonly known as the leukotriene cascade. Leukotrienes are better known for their role in producing inflammation, hyper responsiveness, bronchoconstriction, and increased smooth muscle contraction of the airways; they are able to produce these effects by binding to the cysteinyl leukotriene 1 receptor (CysLT1) . [5].

All leukotrienes involved in the 5-lipoxygenase pathway are synthesized from the fatty acid arachidonic acid[6].; this acid is converted into the intermediate 5-hydroperoxyeicosatetraenioc acid (5-HPETE) by 5-lipoxygenase, and then 5-lipoxygenase quickly converts this into leukotriene A4 (LTA4) [7].LTA4 is a very unstable leukotriene and quickly follows one of two pathways: either its epoxide hydrolase catalyzes the conversion of LTA4 into LTB4, or LTC4 synthase converts it into LTC4 [8]. Each of these leukotrienes precedes their own pathway with LTC4 continuing the cascade to produce subsequent leukotrienes D4 and E4.

Once synthesized in the cytosol of cells within lung tissue, LTC4 is carried by a transmembrane transporter to the extracellular space where it initiates the production of LTD4 and LTE4; leukotrienes C4 and D4 have equal ability to stimulate smooth muscle constriction in the airway, while E4 is not as strong of a muscle constrictor [9]. Each of these leukotrienes can bind to a CysLT receptor producing symptoms associated with asthma and also leading to increased edema formation, mucus secretion, and a decrease in mucus clearance [10]. Montelukast acts as an antagonist by blocking the leukotrienes from binding at the CysLT receptor therefore, preventing the previously discussed symptoms from occurring; it is easy to think of Montelukast as a key that fits into a lock, but does not turn it.

Less information is known about the specifics of how Montelukast may affect the LTB4 pathway; once LTB4 is synthesized from arachidonic acid it is also carried to the extracellular space by a transmembrane transporter; once in the extracellular space it binds to the B leukotriene receptor, known as BLT [11].This leukotriene is a strong neutrophil-chemo-attracting compound that can cause neutrophilic adhesion, mucus generation, and can aid in increasing inflammation seen during asthma [12].It is hypothesized that Montelukast may inhibit 5-lipooxygenase in neutrophils, monocytes, and macrophages possibly preventing the production of LTB4 [13].This mechanism for Montelukast would also be distinct from the mechanism used in the cascade involving leukotriene’s C4, D4, and E4. It is also thought that the amount of Montelukast needed to prevent production of LTB4 would need to be greater than that needed to prevent the CysLT cascade [14].

</StructureSection>

References

  1. ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
  2. ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
  3. ↑ https://www3.rcsb.org/ligand/MTK
  4. ↑ Diamant, Z., Mantzouranis, E., & Bjermer, L. (2009). Montelukast in the treatment of asthma and beyond. Expert Reviews, 5, 639-658. doi:10.1586/eci.09.62
  5. ↑ Nayak, A. (2004). A review of montelukast in the treatment of asthma and allergic rhinitis. Expert Opinion on Pharmacotherapy, 5:3, 679-686. doi:10.1517/14656566.5.3.679
  6. ↑ Drazen, J., Elliot, I., & O’Byrne, P. (1999). Treatment of Asthma with Drugs Modifying the Leukotriene Pathway. The New England Journal of Medicine, 340, 197-206. doi:10.1056/NEJM199901213400306
  7. ↑ Wenzel, S.E. (1997). Arachidonic Acid Metabolites: Mediators of Inflammation in Asthma. Pharmacotherapy, 17, 3S-12S. doi:10.1002/j.1875-9114.1997tbo3696.x
  8. ↑ Wenzel, S.E. (1997). Arachidonic Acid Metabolites: Mediators of Inflammation in Asthma. Pharmacotherapy, 17, 3S-12S. doi:10.1002/j.1875-9114.1997tbo3696.x
  9. ↑ Drazen, J., Elliot, I., & O’Byrne, P. (1999). Treatment of Asthma with Drugs Modifying the Leukotriene Pathway. The New England Journal of Medicine, 340, 197-206. doi:10.1056/NEJM199901213400306
  10. ↑ Wenzel, S.E. (1997). Arachidonic Acid Metabolites: Mediators of Inflammation in Asthma. Pharmacotherapy, 17, 3S-12S. doi:10.1002/j.1875-9114.1997tbo3696.x
  11. ↑ Drazen, J., Elliot, I., & O’Byrne, P. (1999). Treatment of Asthma with Drugs Modifying the Leukotriene Pathway. The New England Journal of Medicine, 340, 197-206. doi:10.1056/NEJM199901213400306
  12. ↑ Wenzel, S.E. (1997). Arachidonic Acid Metabolites: Mediators of Inflammation in Asthma. Pharmacotherapy, 17, 3S-12S. doi:10.1002/j.1875-9114.1997tbo3696.x
  13. ↑ Tintinger, G., Feldman, C., Theron, A., and Anderson, R. (2010) Montelukast:more than a cysteinyl leukotriene receptor antagonist? The Scientific World Journal, 10, 2403-2413. doi:10.1100/tsw.2010.229.
  14. ↑ Tintinger, G., Feldman, C., Theron, A., and Anderson, R. (2010) Montelukast:more than a cysteinyl leukotriene receptor antagonist? The Scientific World Journal, 10, 2403-2413. doi:10.1100/tsw.2010.229.

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