Peroxisome Proliferator-Activated Receptors: Difference between revisions

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

David Canner, Alexander Berchansky, Michal Harel, Joel L. Sussman

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 ==Function==
-The [[Peroxisome Proliferator-Activated Receptors]] (PPAR) α, γ, and δ are members of the nuclear receptor family. Since their discovery in the early 90s, it has become clear that the PPARs are essential modulators of external stimuli, acting as transcription factors to regulate mammalian metabolism, cellular differentiation, and tumorigenesis. The PPARs are the targets of numerous pharmaceutical drugs aimed at treating hypolipidemia and [[diabetes]] among other diseases.<ref name="Berger"/>  See also [[Diabetes & Hypoglycemia]].
+The [[Peroxisome Proliferator-Activated Receptors]] (PPAR) α, γ, and δ are members of the [[Nuclear receptors|nuclear receptor family]]. Since their discovery in the early 90s, it has become clear that the PPARs are essential modulators of external stimuli, acting as transcription factors to regulate mammalian metabolism, cellular differentiation, and tumorigenesis. The PPARs are the targets of numerous pharmaceutical drugs aimed at treating hypolipidemia and [[diabetes]] among other diseases.<ref name="Berger"/>  See also [[Diabetes & Hypoglycemia]].
 *'''PPARα''' regulates the expression of genes involved in fatty acid β oxidation<ref>PMID:15497675</ref>.
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 ==Binding of Synthetic Agonists and Medical Implications==
-A number of synthetic agonists have been developed to bind to <scene name='Peroxisome_Proliferator-Activated_Receptors/Ppar_opening4/2'>PPAR</scene> to fight metabolic diseases like diabetes. These agonists include [http://en.wikipedia.org/wiki/troglitazone troglitazone] ([http://www.rezulin.com Rezulin]), pioglitazone ([[Actos]]), and [[Rosiglitazone]] ([[Avandia]]). These agonists function in a similar fashion, by binding to the active site of PPARγ, activating the receptor. Rosiglitazone occupies roughly 40% of the LBD. It assumes a U-shaped conformation with the TZD head group forming a <scene name='Peroxisome_Proliferator-Activated_Receptors/Rosiglitazone_binding/3'>number of interactions that stabilize the agonist</scene>. Rosiglitazone forms hydrogen bond interactions with H323 and H449 and its TZD group, the sulfur atom of the TZD occupies a hydrophobic pocket formed by Phe363, Glu286, Phe282, Leu330, Ile326 and Leu469, and the central benzene ring occupies a pocket formed by Cys285 and Met364.<ref name="Nolte"/>
+A number of synthetic agonists have been developed to bind to <scene name='Peroxisome_Proliferator-Activated_Receptors/Ppar_opening4/2'>PPAR</scene> to fight metabolic diseases like diabetes. These agonists include [http://en.wikipedia.org/wiki/troglitazone troglitazone] ([http://www.rezulin.com Rezulin]), pioglitazone ([[Actos]]), [[Fenofibrate]] (Tricor) and [[Rosiglitazone]] ([[Avandia]]). These agonists function in a similar fashion, by binding to the active site of PPARγ, activating the receptor. Rosiglitazone occupies roughly 40% of the LBD. It assumes a U-shaped conformation with the TZD head group forming a <scene name='Peroxisome_Proliferator-Activated_Receptors/Rosiglitazone_binding/3'>number of interactions that stabilize the agonist</scene>. Rosiglitazone forms hydrogen bond interactions with H323 and H449 and its TZD group, the sulfur atom of the TZD occupies a hydrophobic pocket formed by Phe363, Glu286, Phe282, Leu330, Ile326 and Leu469, and the central benzene ring occupies a pocket formed by Cys285 and Met364.<ref name="Nolte"/>
 [[Image: Ciprofibrate.PNG|300px|left|thumb| Human PPARα agonist, Ciprofibrate (Modalim)]]
 {{Clear}}