قناة ثالثة بشري (دفعه 52)

🛑🛑 Complex (Compound) Lipids 1. Definition of Complex (Compound) Lipids Complex lipids are esters of fatty acids with alcohols that also contain additional groups such as: • Phosphate • Carbohydrates • Proteins 2. Types of Complex Lipids 1. Phospholipids Composed of: • Fatty acids + alcohol + phosphoric acid + nitrogenous base (e.g. choline, ethanolamine, serine, inositol) They include: • Glycerophospholipids (alcohol = glycerol) • Sphingophospholipids (alcohol = sphingosine) 2. Glycolipids • Lipids that contain carbohydrates 3. Lipoproteins • Lipids conjugated with proteins

وهذا شيت ال cholesterol كمل ♥️.

9. Plasma Cholesterol Levels • Normal total cholesterol: 140–220 mg/dl 10. Hypercholesterolemia Plasma cholesterol > 220 mg/dl Causes • High cholesterol or carbohydrate diet • Hypothyroidism • Diabetes mellitus • Nephrotic syndrome • Obesity • Familial hypercholesterolemia 11. Hypocholesterolemia Plasma cholesterol < 140 mg/dl Causes • Prolonged fasting • Diet rich in unsaturated fatty acids • Liver disease • Hyperthyroidism • Chronic infections

8. Degradation and Excretion of Cholesterol Cholesterol ring cannot be degraded to CO₂ and H₂O. Elimination Pathways 1. Conversion to bile acids 2. Secretion of free cholesterol in bile 3. Intestinal bacterial conversion to: • Coprostanol • Cholestanol → excreted in feces

7. Regulation of Cholesterol Synthesis Regulation mainly occurs at HMG-CoA reductase level. Mechanisms 1. Feedback inhibition • Cholesterol inhibits HMG-CoA reductase activity 2. Gene regulation • Cholesterol suppresses HMG-CoA reductase gene expression 3. Hormonal regulation • Insulin → activates enzyme (dephosphorylation) • Glucagon → inhibits enzyme (via cAMP-dependent kinase) 4. Drug inhibition • Statins (e.g. lovastatin, mevastatin) • Competitive inhibitors • Reduce plasma cholesterol and cardiovascular risk

5. Cholesterol Biosynthesis All 27 carbon atoms of cholesterol are derived from acetyl-CoA. Major Steps 1. Condensation of acetyl-CoA • 2 acetyl-CoA → acetoacetyl-CoA (cytosolic thiolase) • • acetyl-CoA → HMG-CoA (HMG-CoA synthase) 2. Reduction of HMG-CoA to mevalonate • Enzyme: HMG-CoA reductase • Location: Endoplasmic reticulum • Requires NADPH • Rate-limiting and irreversible step • Target of statin drugs ⚠️ Liver contains two HMG-CoA synthase isoenzymes: • Mitochondrial (ketone bodies) • Cytosolic (cholesterol synthesis) 3. Conversion of mevalonate to IPP • Requires 3 ATP • Produces isopentenyl pyrophosphate (IPP) 4. Isomerization • IPP → dimethylallyl pyrophosphate (DMAPP) 5. Formation of isoprenoid units • IPP + DMAPP → geranyl PP (10C) • Geranyl PP + IPP → farnesyl PP (15C) 6. Formation of squalene • 2 farnesyl PP → squalene (30C) • Enzyme: squalene synthase • Pyrophosphate release drives the reaction 7. Cyclization and modification • Squalene → lanosterol • Removal of 3 methyl groups → cholesterol (27C) 6. Packaging and Storage of Cholesterol Most cholesterol is stored as cholesterol esters. Esterification Enzymes 1. ACAT (in cells) • Stores cholesterol as CE 2. LCAT (in plasma) • Associated with HDL • Converts free cholesterol into CE • Facilitates reverse cholesterol transport

4. Cholesterol Balance (Role of Liver) The liver maintains cholesterol homeostasis. Cholesterol Enters the Liver 1. Dietary cholesterol via chylomicron remnants 2. From extra-hepatic tissues via HDL 3. De novo synthesis in the liver Cholesterol Leaves the Liver 1. Secretion in VLDL 2. Free cholesterol secreted into bile 3. Conversion to bile acids and excretion

2. Sources of Cholesterol Cholesterol is obtained from: 1. Dietary sources (animal products: egg yolk, meat, liver, brain) 2. Endogenous synthesis from acetyl-CoA Forms in the Body • Free cholesterol (C) • Cholesterol esters (CE) — storage form Transport in Plasma • Transported in lipoproteins due to hydrophobic nature: • LDL: delivers cholesterol to tissues • HDL: removes cholesterol from tissues and returns it to the liver 3. Tissues Capable of Cholesterol Biosynthesis • Liver (major site) • Intestine • Adrenal cortex • Reproductive tissues Intracellular Location • Cytosol • Endergonic (energy-requiring) pathway

🛑🛑 Cholesterol Metabolism 1. Definition and Functions of Cholesterol Cholesterol is a 27-carbon sterol lipid that is essential for normal body function and must be continuously supplied. Functions • Essential structural component of cell membranes • Precursor of steroid hormones • Precursor of bile acids • Precursor of vitamin D • Major constituent of gallstones

هكي الشيت الخامس كمل ♥️.