CHOLESTEROL METABOLISM

Information about CHOLESTEROL METABOLISM

Published on November 18, 2014

Author: drmustansar

Source: authorstream.com

Content

PowerPoint Presentation: Cholesterol And Sterol Metabolism DR MUHAMMAD MUSTANSAR PowerPoint Presentation: . Lipid metabolism Cholesterol Functions: Cholesterol Functions Membrane component Precurser to Bile acids Vitamin D Steroid hormones Cholesterol PowerPoint Presentation: Dietary cholesterol From chylomicron remnants Cholesterol from extra-hepatic tissues Reverse cholesterol transport via HDL Chylomicron remnants IDL De novo synthesis Central Role of the Liver in Cholesterol Balance: Sources of hepatic cholesterol PowerPoint Presentation: VLDL -> LDL Transport to extra-hepatic tissues Direct excretion into bile Gallstones commonly are precipitates of cholesterol Occurs when bile becomes supersaturated with cholesterol Obesity, biliary stasis, infections Bile acid synthesis and excretion into bile Central Role of the Liver in Cholesterol Balance: Fate of hepatic cholesterol De novo Synthesis of Cholesterol: De novo Synthesis of Cholesterol Primary site: liver (~1g/d) Secondary sites: adrenal cortex, ovaries, testes Overall equation: 18 Acetyl CoA + 18 ATP + 16 NADPH + 4O2 → Cholesterol + 9 CO2 + 16 NADP + + 18 ADP + 18 P i PowerPoint Presentation: Hydroxymethylglutaryl-coenzyme A ( HMG-CoA ) is the precursor for cholesterol synthesis. HMG-CoA is also an intermediate on the pathway for synthesis of ketone bodies from acetyl-CoA. The enzymes for ketone body production are located in the mitochondrial matrix. HMG-CoA destined for cholesterol synthesis is made by equivalent, but different, enzymes in the cytosol . PowerPoint Presentation: HMG-CoA is formed by condensation of acetyl-CoA & acetoacetyl-CoA, catalyzed by HMG-CoA Synthase . HMG-CoA Reductase catalyzes production of mevalonate from HMG-CoA. De novo Synthesis of Cholesterol:four stages: De novo Synthesis of Cholesterol:four stages Formation of HMG CoA (cyto) Analogous to KB synthesis (mito) Conversion of HMG CoA to activated isoprenoids De novo Synthesis of Cholesterol:four stages: De novo Synthesis of Cholesterol:four stages Condensation of isoprenoids to squalene Six isoprenoids condense to form 30-C molecule PowerPoint Presentation: Conversion of Squalene to Cholesterol De novo Synthesis of Cholesterol: four stages PowerPoint Presentation: 18 Acetyl CoA + 18 ATP + 16 NADPH + O 2 → Cholesterol + 9 CO 2 + 16 NADP + + 18 ADP + 18 P i PowerPoint Presentation: Cellular cholesterol content exerts transcriptional control HMG-CoA reductase Half life = 2 hours LDL-receptor synthesis Nutrigenomics: interactions between environment and individual genes and how these interactions affect clinical outcomes Regulation of Cholesterol Synthesis PowerPoint Presentation: Major excretory form of cholesterol Steroid ring is not degraded in humans Occurs in liver Bile acid/salts involved in dietary lipid digestion as emulsifiers Cholesterol and Bile Acid/Salt Metabolism PowerPoint Presentation: Primary bile acids Good emulsifying agents All OH groups on same side pKa = 6 (partially ionized) Conjugated bile salts Amide bonds with glycine or taurine Very good emulsifier pKa lower than bile acids Types of Bile Acids/Salts PowerPoint Presentation: Hydroxylation Cytochrome P-450/mixed function oxidase system Side chain cleavage Conjugation Secondary bile acids Intestinal bacterial modification Deconjugation Dehydroxylation Deoxycholic acid Lithocholic acid Synthesis of Bile Salts PowerPoint Presentation: Enterohepatic circulation 98% recycling of bile acids Cholestyramine Treatment Resin binds bile acids Prevents recycling Increased uptake of LDL-C for bile acid synthesis Recycling of Bile Acids PowerPoint Presentation: Structures of Common statin drugs PowerPoint Presentation: Statin drugs are structural analogs of HMG-CoA PowerPoint Presentation: 8 years old girl Admitted for heart/liver transplant History CHD in family 2 yo xanthomas appear on legs 4 yo xanthomas appear on elbows Case Study – familial hypercholesterolemia PowerPoint Presentation: 7 yo admitted w/ MI symptoms [TC] = 1240 mg/dl [TG] = 350 mg/dl [TC]father = 355 mg/dl [TC]mother = 310 mg/dl 2 wks after MI had coronary bypass surgery Past year severe angina & second bypass Despite low-fat diet, cholestyramine, & lovastatin, [TC] = 1000 mg/dl PowerPoint Presentation: Raised, waxy appearing, often yellow skin lesions (shown here on knee) Associated with hyperlipidemia Tendon xanthomas common on Achilles and hand extensor tendons Xanthomas PowerPoint Presentation: Eruptive Xanthomas -generally associated with hypertriglyceridemia Xanthomas of the eyelid -generally associated with hypercholesterolemia Xanthomas raised lesions related to hyperlipidemia PowerPoint Presentation: Did Da Vinci’s Mona Lisa have hyper-cholesterolemia? PowerPoint Presentation: Aldosterone C21 derivative of cholesterol Promotes renal Sodium retention Potassium excretion Steroid Hormone Metabolism: Adrenal Steroid Hormones PowerPoint Presentation: Glucocorticoids (cortisol) Starvation Hepatic gluconeogenesis Muscle protein degradation Adipose lipolysis Adrenal androgens Dehydroepiandroterone (DHEA) Precurser to potent androgens in extra-adrenal tissues

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