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PHGY 210 (301)
Ann Wechsler (112)
Lecture 6

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PHGY 210
Ann Wechsler

Lecture 6 PXR Ligands and Drug-Drug Interactions Highly expressed in the liver, activity is stimulated by many molecules. Induce drug-drug interactions, these interactions changes the metabolic rate of drugs when multiple different meds are taken. PPARs: Peroxisomal proliferator activated receptors. 3 types, alpha, gamma and delta. PPAR alpha: highly expressed in fatty acid metabolism tissues. PPARA binds fatty acids and their metabolites. Lipids acting as hormonal substances, PPARA then allows for self-regulation of metabolism. PPAR gamma: Expressed in adipose tissue of the intestine and spleen. First high affinity ligand thiazolidinedione (TZD). TZDs are antidiabetic drugs. Used for type 2 diabetes, induce obesity. Induce trafficking of lipids into adipose tissue, removing them from the circulation, body can no longer use them as a source of fuel. Body is then forced to use glucose, which reduces insulin resistance. FXR: named due to binding of farnesyl, an intermediate of cholesterol biosynthesis. Cholesterol controlled by production of CYP7A, enzyme used for conversion of cholesterol into bile acids, feedforward. Feedback blocks bile acid production when con
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