User:Alexander Lee Schmidt/Sandbox 1 - Revision history

Alexander Lee Schmidt at 15:36, 1 December 2016

Alexander Lee Schmidt — Thu, 01 Dec 2016 15:36:14 GMT

←Older revision		Revision as of 15:36, 1 December 2016
Line 10:		Line 10:
	== Function ==		== Function ==
	The mechanism for nitroglycerin breakdown is disputed, but it is know that nitroglycerin eventually breaks down into nitric oxide. In more recent years, nitroglycerin has been found to be broken down with the help of aldehyde dehydrogenase 2 found in the mitochondria. <ref>Mayer, B., and Beretta, M. (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance. News, views, and troubles. Br. J. Pharmacol. 155, 170-184 </ref>		The mechanism for nitroglycerin breakdown is disputed, but it is know that nitroglycerin eventually breaks down into nitric oxide. In more recent years, nitroglycerin has been found to be broken down with the help of aldehyde dehydrogenase 2 found in the mitochondria. <ref>Mayer, B., and Beretta, M. (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance. News, views, and troubles. Br. J. Pharmacol. 155, 170-184 </ref>
-	There has been further proof showing that the breakdown of nitroglycerin permanently alters ALDH2 during (<scene name='74/745476/Cys-~~302_of_aldh2_2~~/1'>Cys-302</scene>) attack <ref name="citation23"> Lang, Barbara S., Antonius Cf Gorren, Gustav Oberdorfer, M. Wenzl, Cristina M. Furdui, Leslie B. Poole, Bernd Mayer, and Karl Gruber. "Vascular Bioactivation of Nitroglycerin: Reaction Mechanism Revealed by Crystal Structure of Aldehyde Dehydrogenase-2." BMC Pharmacology and Toxicology BMC Pharmacol Toxicol 13.Suppl 1 (2012): n. pag. Web. 1 Nov. 2016.</ref>.	+	There has been further proof showing that the breakdown of nitroglycerin permanently alters ALDH2 during <scene name='74/745476/Cys-302_of_aldh2_3/1'>Cys-302</scene> attack <ref name="citation23"> Lang, Barbara S., Antonius Cf Gorren, Gustav Oberdorfer, M. Wenzl, Cristina M. Furdui, Leslie B. Poole, Bernd Mayer, and Karl Gruber. "Vascular Bioactivation of Nitroglycerin: Reaction Mechanism Revealed by Crystal Structure of Aldehyde Dehydrogenase-2." BMC Pharmacology and Toxicology BMC Pharmacol Toxicol 13.Suppl 1 (2012): n. pag. Web. 1 Nov. 2016.</ref>.
	The mechanism that is believed to happen takes nitroglycerin (GTN), bound to aldehyde dehydrogenase 2 (ALDH2) through hydrogen bonds and van der waal interactions of the terminal nitrates, then Cysteine-302 (in ALDH2) attacks GTN to form a thionitrate intermediate while also releasing 1,2-glyceryl dinitrate (1,2-GDN) and a small amount of nitric oxide (NO). The thionitrate is then attacked by the surrounding Cysteines (Cys-301 or Cys-303), which forms a disulfide bond and nitrite. The nitrite is then released and converted into NO. It has also been found that daidzin will inhibit GTN breakdown through competitive inhibition because the binding sites of daidzin and GTN overlap <ref name="citation23"> </ref>. Once NO is released it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref>		The mechanism that is believed to happen takes nitroglycerin (GTN), bound to aldehyde dehydrogenase 2 (ALDH2) through hydrogen bonds and van der waal interactions of the terminal nitrates, then Cysteine-302 (in ALDH2) attacks GTN to form a thionitrate intermediate while also releasing 1,2-glyceryl dinitrate (1,2-GDN) and a small amount of nitric oxide (NO). The thionitrate is then attacked by the surrounding Cysteines (Cys-301 or Cys-303), which forms a disulfide bond and nitrite. The nitrite is then released and converted into NO. It has also been found that daidzin will inhibit GTN breakdown through competitive inhibition because the binding sites of daidzin and GTN overlap <ref name="citation23"> </ref>. Once NO is released it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref>

Alexander Lee Schmidt at 15:24, 1 December 2016

Alexander Lee Schmidt — Thu, 01 Dec 2016 15:24:43 GMT

←Older revision		Revision as of 15:24, 1 December 2016
Line 10:		Line 10:
	== Function ==		== Function ==
	The mechanism for nitroglycerin breakdown is disputed, but it is know that nitroglycerin eventually breaks down into nitric oxide. In more recent years, nitroglycerin has been found to be broken down with the help of aldehyde dehydrogenase 2 found in the mitochondria. <ref>Mayer, B., and Beretta, M. (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance. News, views, and troubles. Br. J. Pharmacol. 155, 170-184 </ref>		The mechanism for nitroglycerin breakdown is disputed, but it is know that nitroglycerin eventually breaks down into nitric oxide. In more recent years, nitroglycerin has been found to be broken down with the help of aldehyde dehydrogenase 2 found in the mitochondria. <ref>Mayer, B., and Beretta, M. (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance. News, views, and troubles. Br. J. Pharmacol. 155, 170-184 </ref>
-	There has been further proof showing that the breakdown of nitroglycerin permanently alters ALDH2 during ~~Cys-302 attack~~(<scene name='74/745476/Cys-~~302_of_aldh2~~/1'>Cys-302 ~~of ALDH2 interacting with Nitroglycerin~~</scene>)<ref name="citation23"> Lang, Barbara S., Antonius Cf Gorren, Gustav Oberdorfer, M. Wenzl, Cristina M. Furdui, Leslie B. Poole, Bernd Mayer, and Karl Gruber. "Vascular Bioactivation of Nitroglycerin: Reaction Mechanism Revealed by Crystal Structure of Aldehyde Dehydrogenase-2." BMC Pharmacology and Toxicology BMC Pharmacol Toxicol 13.Suppl 1 (2012): n. pag. Web. 1 Nov. 2016.</ref>.	+	There has been further proof showing that the breakdown of nitroglycerin permanently alters ALDH2 during (<scene name='74/745476/Cys-302_of_aldh2_2/1'>Cys-302</scene>) attack <ref name="citation23"> Lang, Barbara S., Antonius Cf Gorren, Gustav Oberdorfer, M. Wenzl, Cristina M. Furdui, Leslie B. Poole, Bernd Mayer, and Karl Gruber. "Vascular Bioactivation of Nitroglycerin: Reaction Mechanism Revealed by Crystal Structure of Aldehyde Dehydrogenase-2." BMC Pharmacology and Toxicology BMC Pharmacol Toxicol 13.Suppl 1 (2012): n. pag. Web. 1 Nov. 2016.</ref>.
	The mechanism that is believed to happen takes nitroglycerin (GTN), bound to aldehyde dehydrogenase 2 (ALDH2) through hydrogen bonds and van der waal interactions of the terminal nitrates, then Cysteine-302 (in ALDH2) attacks GTN to form a thionitrate intermediate while also releasing 1,2-glyceryl dinitrate (1,2-GDN) and a small amount of nitric oxide (NO). The thionitrate is then attacked by the surrounding Cysteines (Cys-301 or Cys-303), which forms a disulfide bond and nitrite. The nitrite is then released and converted into NO. It has also been found that daidzin will inhibit GTN breakdown through competitive inhibition because the binding sites of daidzin and GTN overlap <ref name="citation23"> </ref>. Once NO is released it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref>		The mechanism that is believed to happen takes nitroglycerin (GTN), bound to aldehyde dehydrogenase 2 (ALDH2) through hydrogen bonds and van der waal interactions of the terminal nitrates, then Cysteine-302 (in ALDH2) attacks GTN to form a thionitrate intermediate while also releasing 1,2-glyceryl dinitrate (1,2-GDN) and a small amount of nitric oxide (NO). The thionitrate is then attacked by the surrounding Cysteines (Cys-301 or Cys-303), which forms a disulfide bond and nitrite. The nitrite is then released and converted into NO. It has also been found that daidzin will inhibit GTN breakdown through competitive inhibition because the binding sites of daidzin and GTN overlap <ref name="citation23"> </ref>. Once NO is released it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref>

Alexander Lee Schmidt at 15:18, 1 December 2016

Alexander Lee Schmidt — Thu, 01 Dec 2016 15:18:08 GMT

←Older revision		Revision as of 15:18, 1 December 2016
Line 10:		Line 10:
	== Function ==		== Function ==
	The mechanism for nitroglycerin breakdown is disputed, but it is know that nitroglycerin eventually breaks down into nitric oxide. In more recent years, nitroglycerin has been found to be broken down with the help of aldehyde dehydrogenase 2 found in the mitochondria. <ref>Mayer, B., and Beretta, M. (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance. News, views, and troubles. Br. J. Pharmacol. 155, 170-184 </ref>		The mechanism for nitroglycerin breakdown is disputed, but it is know that nitroglycerin eventually breaks down into nitric oxide. In more recent years, nitroglycerin has been found to be broken down with the help of aldehyde dehydrogenase 2 found in the mitochondria. <ref>Mayer, B., and Beretta, M. (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance. News, views, and troubles. Br. J. Pharmacol. 155, 170-184 </ref>
-	There has been further proof showing that the breakdown of nitroglycerin permanently alters ALDH2 during Cys-302 attack <ref name="citation23"> Lang, Barbara S., Antonius Cf Gorren, Gustav Oberdorfer, M. Wenzl, Cristina M. Furdui, Leslie B. Poole, Bernd Mayer, and Karl Gruber. "Vascular Bioactivation of Nitroglycerin: Reaction Mechanism Revealed by Crystal Structure of Aldehyde Dehydrogenase-2." BMC Pharmacology and Toxicology BMC Pharmacol Toxicol 13.Suppl 1 (2012): n. pag. Web. 1 Nov. 2016.</ref>.~~(<scene name='74/745476/Cys-302_of_aldh2/1'>Cys-302 of ALDH2 interacting with Nitroglycerin</scene>)~~	+	There has been further proof showing that the breakdown of nitroglycerin permanently alters ALDH2 during Cys-302 attack(<scene name='74/745476/Cys-302_of_aldh2/1'>Cys-302 of ALDH2 interacting with Nitroglycerin</scene>)<ref name="citation23"> Lang, Barbara S., Antonius Cf Gorren, Gustav Oberdorfer, M. Wenzl, Cristina M. Furdui, Leslie B. Poole, Bernd Mayer, and Karl Gruber. "Vascular Bioactivation of Nitroglycerin: Reaction Mechanism Revealed by Crystal Structure of Aldehyde Dehydrogenase-2." BMC Pharmacology and Toxicology BMC Pharmacol Toxicol 13.Suppl 1 (2012): n. pag. Web. 1 Nov. 2016.</ref>.
	The mechanism that is believed to happen takes nitroglycerin (GTN), bound to aldehyde dehydrogenase 2 (ALDH2) through hydrogen bonds and van der waal interactions of the terminal nitrates, then Cysteine-302 (in ALDH2) attacks GTN to form a thionitrate intermediate while also releasing 1,2-glyceryl dinitrate (1,2-GDN) and a small amount of nitric oxide (NO). The thionitrate is then attacked by the surrounding Cysteines (Cys-301 or Cys-303), which forms a disulfide bond and nitrite. The nitrite is then released and converted into NO. It has also been found that daidzin will inhibit GTN breakdown through competitive inhibition because the binding sites of daidzin and GTN overlap <ref name="citation23"> </ref>. Once NO is released it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref>		The mechanism that is believed to happen takes nitroglycerin (GTN), bound to aldehyde dehydrogenase 2 (ALDH2) through hydrogen bonds and van der waal interactions of the terminal nitrates, then Cysteine-302 (in ALDH2) attacks GTN to form a thionitrate intermediate while also releasing 1,2-glyceryl dinitrate (1,2-GDN) and a small amount of nitric oxide (NO). The thionitrate is then attacked by the surrounding Cysteines (Cys-301 or Cys-303), which forms a disulfide bond and nitrite. The nitrite is then released and converted into NO. It has also been found that daidzin will inhibit GTN breakdown through competitive inhibition because the binding sites of daidzin and GTN overlap <ref name="citation23"> </ref>. Once NO is released it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref>

Alexander Lee Schmidt at 15:12, 1 December 2016

Alexander Lee Schmidt — Thu, 01 Dec 2016 15:12:27 GMT

←Older revision		Revision as of 15:12, 1 December 2016
Line 1:		Line 1:
-	==NitroDur==	+	<scene name='74/745476/Cys-302_of_aldh2/1'>Text To Be Displayed</scene>==NitroDur==

	<StructureSection load='' size='340' side='right' scene='74/745476/Humanaldehydedehydrogenase/1'>		<StructureSection load='' size='340' side='right' scene='74/745476/Humanaldehydedehydrogenase/1'>
Line 10:		Line 10:
	== Function ==		== Function ==
	The mechanism for nitroglycerin breakdown is disputed, but it is know that nitroglycerin eventually breaks down into nitric oxide. In more recent years, nitroglycerin has been found to be broken down with the help of aldehyde dehydrogenase 2 found in the mitochondria. <ref>Mayer, B., and Beretta, M. (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance. News, views, and troubles. Br. J. Pharmacol. 155, 170-184 </ref>		The mechanism for nitroglycerin breakdown is disputed, but it is know that nitroglycerin eventually breaks down into nitric oxide. In more recent years, nitroglycerin has been found to be broken down with the help of aldehyde dehydrogenase 2 found in the mitochondria. <ref>Mayer, B., and Beretta, M. (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance. News, views, and troubles. Br. J. Pharmacol. 155, 170-184 </ref>
-	There has been further proof showing that the breakdown of nitroglycerin permanently alters ALDH2 during Cys-302 attack <ref name="citation23"> Lang, Barbara S., Antonius Cf Gorren, Gustav Oberdorfer, M. Wenzl, Cristina M. Furdui, Leslie B. Poole, Bernd Mayer, and Karl Gruber. "Vascular Bioactivation of Nitroglycerin: Reaction Mechanism Revealed by Crystal Structure of Aldehyde Dehydrogenase-2." BMC Pharmacology and Toxicology BMC Pharmacol Toxicol 13.Suppl 1 (2012): n. pag. Web. 1 Nov. 2016.</ref>.	+	There has been further proof showing that the breakdown of nitroglycerin permanently alters ALDH2 during Cys-302 attack <ref name="citation23"> Lang, Barbara S., Antonius Cf Gorren, Gustav Oberdorfer, M. Wenzl, Cristina M. Furdui, Leslie B. Poole, Bernd Mayer, and Karl Gruber. "Vascular Bioactivation of Nitroglycerin: Reaction Mechanism Revealed by Crystal Structure of Aldehyde Dehydrogenase-2." BMC Pharmacology and Toxicology BMC Pharmacol Toxicol 13.Suppl 1 (2012): n. pag. Web. 1 Nov. 2016.</ref>.(<scene name='74/745476/Cys-302_of_aldh2/1'>Cys-302 of ALDH2 interacting with Nitroglycerin</scene>)
	The mechanism that is believed to happen takes nitroglycerin (GTN), bound to aldehyde dehydrogenase 2 (ALDH2) through hydrogen bonds and van der waal interactions of the terminal nitrates, then Cysteine-302 (in ALDH2) attacks GTN to form a thionitrate intermediate while also releasing 1,2-glyceryl dinitrate (1,2-GDN) and a small amount of nitric oxide (NO). The thionitrate is then attacked by the surrounding Cysteines (Cys-301 or Cys-303), which forms a disulfide bond and nitrite. The nitrite is then released and converted into NO. It has also been found that daidzin will inhibit GTN breakdown through competitive inhibition because the binding sites of daidzin and GTN overlap <ref name="citation23"> </ref>. Once NO is released it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref>		The mechanism that is believed to happen takes nitroglycerin (GTN), bound to aldehyde dehydrogenase 2 (ALDH2) through hydrogen bonds and van der waal interactions of the terminal nitrates, then Cysteine-302 (in ALDH2) attacks GTN to form a thionitrate intermediate while also releasing 1,2-glyceryl dinitrate (1,2-GDN) and a small amount of nitric oxide (NO). The thionitrate is then attacked by the surrounding Cysteines (Cys-301 or Cys-303), which forms a disulfide bond and nitrite. The nitrite is then released and converted into NO. It has also been found that daidzin will inhibit GTN breakdown through competitive inhibition because the binding sites of daidzin and GTN overlap <ref name="citation23"> </ref>. Once NO is released it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref>

Alexander Lee Schmidt at 20:49, 15 November 2016

Alexander Lee Schmidt — Tue, 15 Nov 2016 20:49:01 GMT

←Older revision		Revision as of 20:49, 15 November 2016
Line 3:		Line 3:
	<StructureSection load='' size='340' side='right' scene='74/745476/Humanaldehydedehydrogenase/1'>		<StructureSection load='' size='340' side='right' scene='74/745476/Humanaldehydedehydrogenase/1'>
	==Structure==		==Structure==
-	The main ingredient of NitroDura is 1,2,3-propanetriol trinitrate, also known as <scene name='74/745476/Nitroglycerinmolecule/3'>Nitroglycerin</scene>. Nitroglycerin is a molecule that when broken down to nitric oxide binds to protein domains found in smooth muscle. These binding domains are often found in the form of dimers that require multiple NO molecules to bind as seen in <scene name='74/745476/2o0c_molecule/3'>Nitric Oxide bound to the domain of Nostoc cyanbacterial protein</scene>. The Nitric Oxide is often buried deep within the protein, that in conjunction with other molecular interactions triggers structural changes that activate proteins to serve their specific functions (<scene name='74/745476/2o0c_molecule/3'>NO and CO activating soluble guanylyl cyclase via a heme pivot-bend mechanism.</scene>). In humans, NO binds to protein domains in this same fashion, as seen in <scene name='74/745476/Guanylate_cyclase/1'>Heterodimeric Catalytic Domain of Wild-type Human Soluble Guanylate Cyclase </scene>.	+	The main ingredient of NitroDura is 1,2,3-propanetriol trinitrate, also known as <scene name='74/745476/Nitroglycerinmolecule/3'>Nitroglycerin</scene>. Nitroglycerin is a molecule that when broken down to nitric oxide binds to protein domains found in smooth muscle. These binding domains are often found in the form of dimers that require multiple NO molecules to bind as seen in <scene name='74/745476/2o0c_molecule/3'>Nitric Oxide bound to the domain of Nostoc cyanbacterial protein</scene>. The Nitric Oxide is often buried deep within the protein, that in conjunction with other molecular interactions triggers structural changes that activate proteins to serve their specific functions (<scene name='74/745476/2o0c_molecule/3'>NO and CO activating soluble guanylyl cyclase via a heme pivot-bend mechanism.</scene>). In humans, NO binds to protein domains in this same fashion, as seen in <scene name='74/745476/Guanylate_cyclase/2'>Heterodimeric Catalytic Domain of Wild-type Human Soluble Guanylate Cyclase </scene>.

	==Medication Details==		==Medication Details==

Alexander Lee Schmidt at 20:41, 15 November 2016

Alexander Lee Schmidt — Tue, 15 Nov 2016 20:41:32 GMT

←Older revision		Revision as of 20:41, 15 November 2016
Line 3:		Line 3:
	<StructureSection load='' size='340' side='right' scene='74/745476/Humanaldehydedehydrogenase/1'>		<StructureSection load='' size='340' side='right' scene='74/745476/Humanaldehydedehydrogenase/1'>
	==Structure==		==Structure==
-	The main ingredient of NitroDura is 1,2,3-propanetriol trinitrate, also known as <scene name='74/745476/Nitroglycerinmolecule/3'>Nitroglycerin</scene>. Nitroglycerin is a molecule that when broken down to nitric oxide binds to protein domains found in smooth muscle. These binding domains are often found in the form of dimers that require multiple NO molecules to bind as seen in <scene name='74/745476/2o0c_molecule/2'>Nitric Oxide bound to the domain of Nostoc cyanbacterial protein</scene>. The Nitric Oxide is often buried deep within the protein, that in conjunction with other molecular interactions triggers structural changes that activate proteins to serve their specific functions (<scene name='74/745476/2o0c_molecule/2'>NO and CO activating soluble guanylyl cyclase via a heme pivot-bend mechanism.</scene>). In humans, NO binds to protein domains in this same fashion, as seen in <scene name='74/745476/Guanylate_cyclase/1'>Heterodimeric Catalytic Domain of Wild-type Human Soluble Guanylate Cyclase </scene>.	+	The main ingredient of NitroDura is 1,2,3-propanetriol trinitrate, also known as <scene name='74/745476/Nitroglycerinmolecule/3'>Nitroglycerin</scene>. Nitroglycerin is a molecule that when broken down to nitric oxide binds to protein domains found in smooth muscle. These binding domains are often found in the form of dimers that require multiple NO molecules to bind as seen in <scene name='74/745476/2o0c_molecule/3'>Nitric Oxide bound to the domain of Nostoc cyanbacterial protein</scene>. The Nitric Oxide is often buried deep within the protein, that in conjunction with other molecular interactions triggers structural changes that activate proteins to serve their specific functions (<scene name='74/745476/2o0c_molecule/3'>NO and CO activating soluble guanylyl cyclase via a heme pivot-bend mechanism.</scene>). In humans, NO binds to protein domains in this same fashion, as seen in <scene name='74/745476/Guanylate_cyclase/1'>Heterodimeric Catalytic Domain of Wild-type Human Soluble Guanylate Cyclase </scene>.

	==Medication Details==		==Medication Details==

Alexander Lee Schmidt at 20:29, 15 November 2016

Alexander Lee Schmidt — Tue, 15 Nov 2016 20:29:14 GMT

←Older revision		Revision as of 20:29, 15 November 2016
Line 1:		Line 1:
	==NitroDur==		==NitroDur==

-	<StructureSection load='~~4fr8~~' size='340' side='right' scene=''>	+	<StructureSection load='' size='340' side='right' scene='74/745476/Humanaldehydedehydrogenase/1'>
	==Structure==		==Structure==
	The main ingredient of NitroDura is 1,2,3-propanetriol trinitrate, also known as <scene name='74/745476/Nitroglycerinmolecule/3'>Nitroglycerin</scene>. Nitroglycerin is a molecule that when broken down to nitric oxide binds to protein domains found in smooth muscle. These binding domains are often found in the form of dimers that require multiple NO molecules to bind as seen in <scene name='74/745476/2o0c_molecule/2'>Nitric Oxide bound to the domain of Nostoc cyanbacterial protein</scene>. The Nitric Oxide is often buried deep within the protein, that in conjunction with other molecular interactions triggers structural changes that activate proteins to serve their specific functions (<scene name='74/745476/2o0c_molecule/2'>NO and CO activating soluble guanylyl cyclase via a heme pivot-bend mechanism.</scene>). In humans, NO binds to protein domains in this same fashion, as seen in <scene name='74/745476/Guanylate_cyclase/1'>Heterodimeric Catalytic Domain of Wild-type Human Soluble Guanylate Cyclase </scene>.		The main ingredient of NitroDura is 1,2,3-propanetriol trinitrate, also known as <scene name='74/745476/Nitroglycerinmolecule/3'>Nitroglycerin</scene>. Nitroglycerin is a molecule that when broken down to nitric oxide binds to protein domains found in smooth muscle. These binding domains are often found in the form of dimers that require multiple NO molecules to bind as seen in <scene name='74/745476/2o0c_molecule/2'>Nitric Oxide bound to the domain of Nostoc cyanbacterial protein</scene>. The Nitric Oxide is often buried deep within the protein, that in conjunction with other molecular interactions triggers structural changes that activate proteins to serve their specific functions (<scene name='74/745476/2o0c_molecule/2'>NO and CO activating soluble guanylyl cyclase via a heme pivot-bend mechanism.</scene>). In humans, NO binds to protein domains in this same fashion, as seen in <scene name='74/745476/Guanylate_cyclase/1'>Heterodimeric Catalytic Domain of Wild-type Human Soluble Guanylate Cyclase </scene>.

Alexander Lee Schmidt at 20:10, 15 November 2016

Alexander Lee Schmidt — Tue, 15 Nov 2016 20:10:49 GMT

←Older revision		Revision as of 20:10, 15 November 2016
Line 1:		Line 1:
	==NitroDur==		==NitroDur==

-	<StructureSection load='4fr8' size='340' side='right~~' caption='4FR8 Crystal structure of human aldehyde dehydrogenase-2 in complex with nitroglycerin~~' scene=''>	+	<StructureSection load='4fr8' size='340' side='right' scene=''>
	==Structure==		==Structure==
-	The main ingredient of NitroDura is 1,2,3-propanetriol trinitrate, also known as <scene name='74/745476/Nitroglycerinmolecule/1'>Nitroglycerin</scene>. Nitroglycerin is a molecule that when broken down to nitric oxide binds to protein domains found in smooth muscle. These binding domains are often found in the form of dimers that require multiple NO molecules to bind as seen in <scene name='74/745476/2o0c_molecule/2'>Nitric Oxide bound to the domain of Nostoc cyanbacterial protein</scene>. The Nitric Oxide is often buried deep within the protein, that in conjunction with other molecular interactions triggers structural changes that activate proteins to serve their specific functions (<scene name='74/745476/2o0c_molecule/2'>NO and CO activating soluble guanylyl cyclase via a heme pivot-bend mechanism.</scene>). In humans, NO binds to protein domains in this same fashion, as seen in <scene name='74/745476/Guanylate_cyclase/1'>Heterodimeric Catalytic Domain of Wild-type Human Soluble Guanylate Cyclase </scene>.	+	The main ingredient of NitroDura is 1,2,3-propanetriol trinitrate, also known as <scene name='74/745476/Nitroglycerinmolecule/3'>Nitroglycerin</scene>. Nitroglycerin is a molecule that when broken down to nitric oxide binds to protein domains found in smooth muscle. These binding domains are often found in the form of dimers that require multiple NO molecules to bind as seen in <scene name='74/745476/2o0c_molecule/2'>Nitric Oxide bound to the domain of Nostoc cyanbacterial protein</scene>. The Nitric Oxide is often buried deep within the protein, that in conjunction with other molecular interactions triggers structural changes that activate proteins to serve their specific functions (<scene name='74/745476/2o0c_molecule/2'>NO and CO activating soluble guanylyl cyclase via a heme pivot-bend mechanism.</scene>). In humans, NO binds to protein domains in this same fashion, as seen in <scene name='74/745476/Guanylate_cyclase/1'>Heterodimeric Catalytic Domain of Wild-type Human Soluble Guanylate Cyclase </scene>.

	==Medication Details==		==Medication Details==

Alexander Lee Schmidt at 15:17, 13 November 2016

Alexander Lee Schmidt — Sun, 13 Nov 2016 15:17:47 GMT

←Older revision		Revision as of 15:17, 13 November 2016
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	The mechanism for nitroglycerin breakdown is disputed, but it is know that nitroglycerin eventually breaks down into nitric oxide. In more recent years, nitroglycerin has been found to be broken down with the help of aldehyde dehydrogenase 2 found in the mitochondria. <ref>Mayer, B., and Beretta, M. (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance. News, views, and troubles. Br. J. Pharmacol. 155, 170-184 </ref>		The mechanism for nitroglycerin breakdown is disputed, but it is know that nitroglycerin eventually breaks down into nitric oxide. In more recent years, nitroglycerin has been found to be broken down with the help of aldehyde dehydrogenase 2 found in the mitochondria. <ref>Mayer, B., and Beretta, M. (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance. News, views, and troubles. Br. J. Pharmacol. 155, 170-184 </ref>
	There has been further proof showing that the breakdown of nitroglycerin permanently alters ALDH2 during Cys-302 attack <ref name="citation23"> Lang, Barbara S., Antonius Cf Gorren, Gustav Oberdorfer, M. Wenzl, Cristina M. Furdui, Leslie B. Poole, Bernd Mayer, and Karl Gruber. "Vascular Bioactivation of Nitroglycerin: Reaction Mechanism Revealed by Crystal Structure of Aldehyde Dehydrogenase-2." BMC Pharmacology and Toxicology BMC Pharmacol Toxicol 13.Suppl 1 (2012): n. pag. Web. 1 Nov. 2016.</ref>.		There has been further proof showing that the breakdown of nitroglycerin permanently alters ALDH2 during Cys-302 attack <ref name="citation23"> Lang, Barbara S., Antonius Cf Gorren, Gustav Oberdorfer, M. Wenzl, Cristina M. Furdui, Leslie B. Poole, Bernd Mayer, and Karl Gruber. "Vascular Bioactivation of Nitroglycerin: Reaction Mechanism Revealed by Crystal Structure of Aldehyde Dehydrogenase-2." BMC Pharmacology and Toxicology BMC Pharmacol Toxicol 13.Suppl 1 (2012): n. pag. Web. 1 Nov. 2016.</ref>.
-	The mechanism that is believed to happen takes nitroglycerin (GTN), bound to aldehyde dehydrogenase 2 (ALDH2) through hydrogen bonds and van der waal interactions of the terminal nitrates, then Cysteine-302 (in ALDH2) attacks GTN to form a thionitrate intermediate while also releasing 1,2-glyceryl dinitrate (1,2-GDN) and a small amount of nitric oxide (NO). The thionitrate is then attacked by the surrounding Cysteines (Cys-301 or Cys-303), which forms a disulfide bond and nitrite. The nitrite is then released and converted into NO. It has also been found that daidzin will inhibit GTN breakdown through competitive inhibition because the binding sites of daidzin and GTN overlap <ref name="citation23"> </ref>.	+	The mechanism that is believed to happen takes nitroglycerin (GTN), bound to aldehyde dehydrogenase 2 (ALDH2) through hydrogen bonds and van der waal interactions of the terminal nitrates, then Cysteine-302 (in ALDH2) attacks GTN to form a thionitrate intermediate while also releasing 1,2-glyceryl dinitrate (1,2-GDN) and a small amount of nitric oxide (NO). The thionitrate is then attacked by the surrounding Cysteines (Cys-301 or Cys-303), which forms a disulfide bond and nitrite. The nitrite is then released and converted into NO. It has also been found that daidzin will inhibit GTN breakdown through competitive inhibition because the binding sites of daidzin and GTN overlap <ref name="citation23"> </ref>. Once NO is released it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref>
-		+
-	Once NO is released it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref>	+

	== Disease ==		== Disease ==
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	===Raynaud’s Phenomenon===		===Raynaud’s Phenomenon===
-	The Raynaud's pehnomenon occurs due to vasoconstriction of the capillaries, veins, and arteries in external digits <ref name="citation2"> <ref>PMCID: PMC2860448</ref>. Symptoms of raynaud’s involves the fingers or toes turning pale, becoming numb, and then ~~becoming~~ purple or blue. These symptoms result from attacks that ~~can~~ are characterized by spasms in the small blood vessels of the fingers and toes <ref>Haythornthwaite, Jenifer, Dr., and Fredrick Wigley, Dr. "Raynaud's, Finger and Skin Care." Scleroderma Education Program Chapter 2 Raynaud’s, Finger and Skin Care (n.d.): n. pag. Web. 16 Oct. 2016 </ref>. Patients who have been diagnosed with Raynaud’s phenomenon will occasionally need ~~pharmacologic~~ therapy. While the nitro-dur patch is not specifically ~~used~~, topical nitroglycerin ~~can be prescribed to~~ these patients ~~and decreases~~ the occurrence and severity of vasospastic episodes <ref name="citation2"> </ref>. Nitroglycerin does this by expanding the blood vessels allowing blood ~~to better circulate~~ <ref name="citation3"> </ref>.	+	The Raynaud's pehnomenon occurs due to vasoconstriction of the capillaries, veins, and arteries in external digits <ref name="citation2"> <ref>PMCID: PMC2860448</ref>. Symptoms of raynaud’s involves the fingers or toes turning pale, becoming numb, and then transitioning to a shade of purple or blue. These symptoms result from attacks that are characterized by spasms in the small blood vessels of the fingers and toes <ref>Haythornthwaite, Jenifer, Dr., and Fredrick Wigley, Dr. "Raynaud's, Finger and Skin Care." Scleroderma Education Program Chapter 2 Raynaud’s, Finger and Skin Care (n.d.): n. pag. Web. 16 Oct. 2016 </ref>. Patients who have been diagnosed with Raynaud’s phenomenon will occasionally need pharmacological therapy. While the nitro-dur patch is not specifically precribe, topical nitroglycerin ointment is used on these patients to decrease the occurrence and severity of vasospastic episodes <ref name="citation2"> </ref>. Nitroglycerin does this by expanding the blood vessels allowing better blood circulation <ref name="citation3"> </ref>.

	</StructureSection>		</StructureSection>

Alexander Lee Schmidt at 15:12, 13 November 2016

Alexander Lee Schmidt — Sun, 13 Nov 2016 15:12:30 GMT

←Older revision		Revision as of 15:12, 13 November 2016
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	Once NO is released it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref>		Once NO is released it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref>

-	Nitroglycerin is commonly used to treat various conditions involving the heart. It used to increase the chances of detecting coronary artery disease when using MR coronary artery imaging (MRCA). Nitroglycerin increases the vessel length allowing coronary artery disease to be more visible under MRCA <ref name="citation3">PMID: 27731913</ref>. Nitroglycerin is also used to treat heart disease and angina which is classified as heart pain. Angina is caused by inadequate flow of oxygen and blood to the heart. To prevent this problem, nitroglycerin is used and will open up the blood vessels. This widening of the blood vessels allows the heart to do less work requiring less oxygen and blood <ref name="citation2"> </ref>.
	== Disease ==		== Disease ==

	===Heart Disease===		===Heart Disease===
-	Nitroglycerin is commonly used to treat various conditions involving the heart. One way it's used is to increase the chances of detecting coronary artery disease when using MR coronary artery imaging (MRCA). This is done by increasing the vessel length ~~allowing~~ coronary artery disease ~~to be~~ more visible under MRCA <ref name="citation3"> </ref>. Nitroglycerin is also used to treat heart disease and angina, which is classified as heart pain. Angina is caused by the heart ~~being unable to meet it's oxygen demands with it's current blood oxygen supply~~. To alleviate this problem, nitroglycerin is ~~used~~ to widen the blood vessels reducing the heart's workload and thus oxygen demands from the blood supply <ref name="citation2"> </ref>.	+	Nitroglycerin is commonly used to treat various conditions involving the heart. One way it's used is to increase the chances of detecting coronary artery disease when using MR coronary artery imaging (MRCA). This is done by increasing the vessel length making coronary artery disease more visible under MRCA <ref name="citation3">PMID: 27731913</ref>. Nitroglycerin is also used to treat heart disease and angina, which is classified as heart pain. Angina is caused by an inadequate supply of oxygen in the blood that flows to heart. To alleviate this problem, nitroglycerin is administered to widen the blood vessels reducing the heart's workload and thus oxygen demands from the oxygen poor blood supply <ref name="citation2"> </ref>.

	===Chronic Achilles Tendinopathy===		===Chronic Achilles Tendinopathy===