Cholesterol Metabolism PDF

Cholesterol Metabolism Learning Outcomes Appraise the steps involved in the synthesis and isᵗ8ⁿᵈwed degradation of cholesterol...

Cholesterol Metabolism Learning Outcomes Appraise the steps involved in the synthesis and isᵗ8ⁿᵈwed degradation of cholesterol mm Normal Blood level and Correlate to hyper is 150-200 mg% cholesterolemia Wcted all steriod are derived from cholesterol What is cholesterol ? It is a elipid , a sterol knmpisfg.tn ofcell membrane it'smaintaintheFluid It is an essential component of most biological membranes, and required for synthesis of biologically important compounds May cause atherosclerotic vascular disease thinness anati No vegetable oil contains any cholesterol. the bloodflew  Cholesterol Background Synthesis Obtained through diet or synthesis ( 20 %) D Synthesized in many cells, but am mostly in the liver (intestine ,adrenal cortex & testis,overies) All Humans synthesize approximately 1 g/day A typical Western diet For 27 Carbon contains appro. 500 mg atom subcellular site involved in synthesist daily, mainly in meat, eggs, and Site: Cytosol and ER of cho we in dairy products the cell. To rich in cholesterol  How is Cholesterol Synthesized? cholesterol is derived from 2L Comes From Acyl choline Precursor :Acetyl CoA which is obtained from: 1.Pyruvate dehydrogenase reaction (Pyruvate to Acetyl CoA) 2.β-oxidation of Fatty acids or from break down of amino acids eWbeakdownffatty T E pyruvate ductiveSaftusis google.pe2NADPH+H+ pyruvate Acetyl in glucose sourcefor enzyme 2NADP synthesis Ace 3 carbon atom being compindT form Ratelimiting Lenzyme For cholesterol D synthesis HMG CoA reductase is the rate limiting enzyme. Competitive inhibitor inhibitcholesterol synthesis of HMG CoA Reductase – statins like simvastatin, fluvastatin are used to treat increased blood cholesterol How is cholesterol Synthesis regulated? HMC7 CoA reductase is inhibited by Cholesterol, , steroid hormones synthesisof Glucagon, glucocorticoids. MRNAfrom the Stimulated by insulin , estrogen one gene reductase stimulate HMGCoA insulin + HMG Co A HMG CoA Tattwhenydrate -- reductase glucagon/ HMG CoA glucocorticoids -- reductase Inhibit HMGreductase feed back repression of enzyme HMG Co A reductase by MEVOLANATE cholesterol to prevent Cholesterol Tthegin excess production. t the HMG reductase enzyme  SRE gene name Regulation by Sterol regulatory element- SREBPs are synthesized as binding protein (SREBP) inactive precursors that exist in the endoplasmic reticulum (ER) membrane. In cholesterol deficiency SREBP cleavage activating protein (SCAP) escorts SREBPs from the ER to the Golgi where proteases release the NH2-teminal region of SREBPs. The NH2-teminal region of SREBPs moves to the nucleus and binds to the sterol regulatory element(SRE) of the LDL receptor gene and of enzymes of cholesterol synthesis → increased transcription of LDL receptors and HMG Co A reductase → increased uptake and synthesis of cholesterol Synthesis of following require cholesterol compoundmade from cheek Bile acids-( 80% cholesterol is converted to Bile acids in liver ) cholic I acid and chenodeoxycholic acid are called primary bile acids.Bile acids are required for digestion& absorption of fats and lipidsthatpnrsen. Bile acid sequestrant are given for hypercholesterolemia they bind dnqnetytifneE.th to bile acids in the intestine to increase their excretion Steroid hormones (corticosteroids , mineralocorticoids, estrogens) Vitamin D Cell Membranes Biliary cholesterol Cholesterol ester -Acyl-CoA: cholesterol of acyl transferase (ACAT) an ER membrane enzyme transfers fatty acid to cholesterol. a Excess cholesterol is stored as cholesterol esters. Intera cholestero Faith  bile acid goesto the gallbladder from gallbladder so ainenzymerequiredto convertcholestonto bill Bile acids are goestotheintestine required for digestion absorption of fats / lipids the CHOLIC ACID III CHENODEOXYCHOLIC ACID approx 5 is 10 in the fecalma andremainingis Live transport back to  Diabetes and Cholesterol Conditions associated with increased serum cholesterol ? 1.Insulin Resistance or Deficiency ↓ Diabetes 2.↑ Lipolysis (Increased breakdown of Obstructive jaundice fats in adipose tissue) ↓ Hypothyroidism 3.↑ Free Fatty Acids in Blood & thus ↑ Nephrotic syndrome acetyl Co A Familial ↓ hyperlipoproteinemia (↑LDL) 4.↑ Cholesterol Synthesis in Liver Increases cholesterol Also ↓ Clearance of LDL (Impaired deposition in blood vessel lipoprotein metabolism) walls causes ↓ Atherosclerosis ↑ Accumulation of LDL in Bloodstream LDL transports cholesterol from the liver to peripheral tissues. HDL transports cholesterol from tissues to liver  Obstructive Jaundice Hypothyroidism and Cholesterol ↓ Blocked Bile Ducts (Cholestasis) ↓ 1.Hypothyroidism ↓ Bile Flow ↓ ↓ 2.↓ Thyroid Hormones ↓ Conversion of Cholesterol to Bile ↓ Acids 3.↓ LDL Receptor Activity (Slows LDL ↓ clearance from blood) ↑ Cholesterol Accumulation in Blood ↓ 4.↑ LDL Cholesterol in Blood (Accumulation of LDL) Nephrotic Syndrome and Cholesterol Nephrotic Syndrome ↓ Also ↓ Conversion of Cholesterol to 1.Significant Proteinuria (Loss of Bile Acids due to thyroid hormone albumin and proteins in urine) deficiency ↓ ↓ 2.↓ Albumin (Hypoalbuminemia) ↑ Cholesterol Accumulation in ↓ Bloodstream 3.↑ Liver Production of Lipoproteins (Increased VLDL, LDL)