User:Sachin Sundar/Sandbox 1: Difference between revisions

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As Lovastatin is ingested after being taken orally, water inside an individual's body will hydrolyze this lactone into its β-hydroxyacid form. <ref name= "two"> Mevacor (Lovastatin). (2014, February). Retrieved March 28, 2017, from https://www.merck.com/product/usa/pi_circulars/m/mevacor/mevacor_pi.pdf<ref/>

This metabolite is crucial as it is the active form of the inhibitor. The β-hydroxyacid moiety is structurally similar to the HMG moiety of the substrate HMG-CoA, and both moieties form strong hydrogen bonds to the active site on the HMG-CoA reductase <ref name= "fifteen">http://www.jbc.org/content/278/22/19933.long#F4

Tabernero‡§, L.; and, V. W. R. Lydia Tabernero http://www.jbc.org/content/278/22/19933.long#F4 (accessed Apr 20, 2017).<ref/> As food is digested, it is normally taken to the liver where it is further broken down in order to produce cholesterol, or fuel for an individual’s body. To begin the biosynthesis pathway of cholesterol, Acetyl-CoA is first produced in the process of breaking down the ingested food. Acetyl-CoA will become cholesterol through several biochemical steps, and the most important point in this process is the rate-limiting step known as HMG-CoA (3-hydroxy-methylglutarylcoenzyme A) reductase. This enzyme is considered to be the rate limiting step because it can stop the process of forming Mevalonate, which is the main reason for the biosynthesis pathway to continue. Due to this important information, statins target the HMG-CoA reductase enzyme in order to inhibit the biosynthesis pathway. As Lovastatin binds to the reductase, this lowers the production of cholesterol in the liver. When cholesterol levels become low, this initiates an active protease to cleave sterol regulatory element-binding proteins (SREBP) in the endoplasmic reticulum. The nucleus detects the cleavage, and increases the expression of the LDL receptor gene causing an increase of LDL receptors to the cell surface. This will then increase the receptor-mediated endocytosis of LDL, causing LDL levels from the blood to lower. This process also increases HDL and decreases triglycerides in the plasmid. <ref name= "two"/>

Tabernero‡§, L.; and, V. W. R. Lydia Tabernero http://www.jbc.org/content/278/22/19933.long#F4 (accessed Apr 20, 2017).<ref/> As food is digested, it is normally taken to the liver where it is further broken down in order to produce cholesterol, or fuel for an individual’s body. To begin the biosynthesis pathway of cholesterol, Acetyl-CoA is first produced in the process of breaking down the ingested food. Acetyl-CoA will become cholesterol through several biochemical steps, and the most important point in this process is the rate-limiting step known as HMG-CoA (3-hydroxy-methylglutarylcoenzyme A) reductase. This enzyme is considered to be the rate limiting step because it can stop the process of forming Mevalonate, which is the main reason for the biosynthesis pathway to continue. Due to this important information, statins target the HMG-CoA reductase enzyme in order to inhibit the biosynthesis pathway. As Lovastatin binds to the reductase, this lowers the production of cholesterol in the liver. When cholesterol levels become low, this initiates an active protease to cleave sterol regulatory element-binding proteins (SREBP) in the endoplasmic reticulum. The nucleus detects the cleavage, and increases the expression of the LDL receptor gene causing an increase of LDL receptors to the cell surface. This will then increase the receptor-mediated endocytosis of LDL, causing LDL levels from the blood to lower. This process also increases HDL and decreases triglycerides in the plasmid. <ref name="two"/>

== Structure ==

Lovastatin mimics the binding of HMG-CoA substrate, therefore it is confirmed that these two structures are similar. The molecular formula of Lovastatin is C24H36O5 and the molecular weight is 405 Da <ref name= "nine">Masterjohn, C. (2005, July). Cholesterol's Importance to the Cell Membrane. Retrieved March 28, 2017, from http://www.cholesterol-and-health.com/Cholesterol-Cell-Membrane.html</ref>. Lovastatin is in a lactone ring conformation when in the inactivated form. Lactones are cyclic esters, or a ring consisting of two or more carbon atoms and one oxygen atom with a ketone group located on one of the carbons adjacent to the other oxygen <ref name= "sixteen">http://www.sigmaaldrich.com/chemistry/chemistry-products.html?TablePage=16270948

Lovastatin mimics the binding of HMG-CoA substrate, therefore it is confirmed that these two structures are similar. The molecular formula of Lovastatin is C24H36O5 and the molecular weight is 405 Da. <ref name="nine">Masterjohn, C. (2005, July). Cholesterol's Importance to the Cell Membrane. Retrieved March 28, 2017, from http://www.cholesterol-and-health.com/Cholesterol-Cell-Membrane.html</ref> Lovastatin is in a lactone ring conformation when in the inactivated form. Lactones are cyclic esters, or a ring consisting of two or more carbon atoms and one oxygen atom with a ketone group located on one of the carbons adjacent to the other oxygen <ref name= "sixteen">http://www.sigmaaldrich.com/chemistry/chemistry-products.html?TablePage=16270948

Chemistry Products No delete http://www.sigmaaldrich.com/chemistry/chemistry-products.html?TablePage=16270948 (accessed Apr 20, 2017)<ref/>

[[Media:lov2d.jpg|(Image of Lovastatin 2D Structure)]]. Hydroxymethylglutaryl-CoA (HMG-CoA) is an intermediate in the mevalonate pathway with a molecular formula of C27H44N7O20P3S and a molecular weight of 911.659 g/mol <ref name= "nineteen"> https://pubchem.ncbi.nlm.nih.gov/compound/445127

@@ Line 14: / Line 14: @@
 As Lovastatin is ingested after being taken orally, water inside an individual's body will hydrolyze this lactone into its β-hydroxyacid form. <ref name= "two"> Mevacor (Lovastatin). (2014, February). Retrieved March 28, 2017, from https://www.merck.com/product/usa/pi_circulars/m/mevacor/mevacor_pi.pdf<ref/>
 This metabolite is crucial as it is the active form of the inhibitor. The β-hydroxyacid moiety is structurally similar to the HMG moiety of the substrate HMG-CoA, and both moieties form strong hydrogen bonds to the active site on the HMG-CoA reductase <ref name= "fifteen">http://www.jbc.org/content/278/22/19933.long#F4
-Tabernero‡§, L.; and, V. W. R. Lydia Tabernero http://www.jbc.org/content/278/22/19933.long#F4 (accessed Apr 20, 2017).<ref/> As food is digested, it is normally taken to the liver where it is further broken down in order to produce cholesterol, or fuel for an individual’s body. To begin the biosynthesis pathway of cholesterol, Acetyl-CoA is first produced in the process of breaking down the ingested food. Acetyl-CoA will become cholesterol through several biochemical steps, and the most important point in this process is the rate-limiting step known as HMG-CoA (3-hydroxy-methylglutarylcoenzyme A) reductase. This enzyme is considered to be the rate limiting step because it can stop the process of forming Mevalonate, which is the main reason for the biosynthesis pathway to continue. Due to this important information, statins target the HMG-CoA reductase enzyme in order to inhibit the biosynthesis pathway.  As Lovastatin binds to the reductase, this lowers the production of cholesterol in the liver. When cholesterol levels become low, this initiates an active protease to cleave sterol regulatory element-binding proteins (SREBP) in the endoplasmic reticulum. The nucleus detects the cleavage, and increases the expression of the LDL receptor gene causing an increase of LDL receptors to the cell surface. This will then increase the receptor-mediated endocytosis of LDL, causing LDL levels from the blood to lower. This process also increases HDL and decreases triglycerides in the plasmid. <ref name= "two"/>
+Tabernero‡§, L.; and, V. W. R. Lydia Tabernero http://www.jbc.org/content/278/22/19933.long#F4 (accessed Apr 20, 2017).<ref/> As food is digested, it is normally taken to the liver where it is further broken down in order to produce cholesterol, or fuel for an individual’s body. To begin the biosynthesis pathway of cholesterol, Acetyl-CoA is first produced in the process of breaking down the ingested food. Acetyl-CoA will become cholesterol through several biochemical steps, and the most important point in this process is the rate-limiting step known as HMG-CoA (3-hydroxy-methylglutarylcoenzyme A) reductase. This enzyme is considered to be the rate limiting step because it can stop the process of forming Mevalonate, which is the main reason for the biosynthesis pathway to continue. Due to this important information, statins target the HMG-CoA reductase enzyme in order to inhibit the biosynthesis pathway.  As Lovastatin binds to the reductase, this lowers the production of cholesterol in the liver. When cholesterol levels become low, this initiates an active protease to cleave sterol regulatory element-binding proteins (SREBP) in the endoplasmic reticulum. The nucleus detects the cleavage, and increases the expression of the LDL receptor gene causing an increase of LDL receptors to the cell surface. This will then increase the receptor-mediated endocytosis of LDL, causing LDL levels from the blood to lower. This process also increases HDL and decreases triglycerides in the plasmid. <ref name="two"/>
 == Structure ==
-Lovastatin mimics the binding of HMG-CoA substrate, therefore it is confirmed that these two structures are similar. The molecular formula of Lovastatin is C24H36O5 and the molecular weight is 405 Da <ref name= "nine">Masterjohn, C. (2005, July). Cholesterol's Importance to the Cell Membrane. Retrieved March 28, 2017, from http://www.cholesterol-and-health.com/Cholesterol-Cell-Membrane.html</ref>. Lovastatin is in a lactone ring conformation when in the inactivated form. Lactones are cyclic esters, or a ring consisting of two or more carbon atoms and one oxygen atom with a ketone group located on one of the carbons adjacent to the other oxygen <ref name= "sixteen">http://www.sigmaaldrich.com/chemistry/chemistry-products.html?TablePage=16270948
+Lovastatin mimics the binding of HMG-CoA substrate, therefore it is confirmed that these two structures are similar. The molecular formula of Lovastatin is C24H36O5 and the molecular weight is 405 Da. <ref name="nine">Masterjohn, C. (2005, July). Cholesterol's Importance to the Cell Membrane. Retrieved March 28, 2017, from http://www.cholesterol-and-health.com/Cholesterol-Cell-Membrane.html</ref> Lovastatin is in a lactone ring conformation when in the inactivated form. Lactones are cyclic esters, or a ring consisting of two or more carbon atoms and one oxygen atom with a ketone group located on one of the carbons adjacent to the other oxygen <ref name= "sixteen">http://www.sigmaaldrich.com/chemistry/chemistry-products.html?TablePage=16270948
 Chemistry Products No delete http://www.sigmaaldrich.com/chemistry/chemistry-products.html?TablePage=16270948 (accessed Apr 20, 2017)<ref/>
   [[Media:lov2d.jpg|(Image of Lovastatin 2D Structure)]].  Hydroxymethylglutaryl-CoA (HMG-CoA) is an intermediate in the mevalonate pathway with a molecular formula of C27H44N7O20P3S and a molecular weight of 911.659 g/mol <ref name= "nineteen"> https://pubchem.ncbi.nlm.nih.gov/compound/445127