Lipids Metabolism - Chapter 6 - Pr. LAHLOU - 2024-2025 PDF

Lipids metabolism Pr. Fatima Azzahra LAHLOU Chapter 6 Module: Biochemistry Academic Year : 2024-2025 www.um6ss.ma  Plan Introduction...

Lipids metabolism Pr. Fatima Azzahra LAHLOU Chapter 6 Module: Biochemistry Academic Year : 2024-2025 www.um6ss.ma  Plan Introduction Definition Catabolism Phospholipis Triglycerides Fatty acids Ketone bodies Anabolism Fatty acids Phospholipids Triglycerides Cholesterol Cholesterol derivatives 2 Learning Objectives  Know what is a lipolysis  Understand lipids catabolism  Understand lipids anabolim  Know the derivatives of cholesterol  Know the ketone bodies FACULTY OF MEDICINE – UM6SS – CASABLANCA Introduction Phospholipids 4  Phospholipids catabolism Lipolysis = metabolic process through which lipids (TG/PL/FA) break down via hydrolysis into their constituent molecules  Phospholipids hydrolysis: phoslipases A1, A2, C and D 5  Phospholipids catabolism Phospholipids hydrolysis: phoslipases A1, A2, C and D  It generates:  Cellular mediators (cell signaling as second messenger): Inositon tri-phosphate (IP3), diacylglycerol (DAG), phosphatidic acid (PA)  Free fatty acids as arachidonc acid (prostaglandins…)/ATP production  Remodeling of cellular membranes 6  Triglycerides catabolism Exogenous triglycerides hydrolysis (incomplete): 7  Triglycerides catabolism Endogenous triglycerides hydrolysis (complete): 8  Fatty acids catabolism Lipolysis: Beta-oxydation Glycolysis 9  Fatty acids catabolism Fatty acids catabolism leads to ATP production trough:  Activation  Transport  Beta-oxidation 10  Fatty acids catabolism Fatty acids catabolism leads to ATP production trough:  Activation: 2 ATP consumed Activated FA 11  Fatty acids catabolism Fatty acids catabolism leads to ATP protection trough:  Transport: Carnitine activated FA Beta-oxidation 12  Fatty acids catabolism Fatty acids catabolism leads to ATP production trough:  Beta-oxidation LYNEN helix FEODOR LYNEN 13  Fatty acids catabolism Fatty acids catabolism leads to ATP protection trough:  Beta-oxidation - Dehydrogenation - Hydratation - Dehydrogenation - Thiolysis 14  Fatty acids catabolism Fatty acids catabolism leads to ATP production trough: 15  Fatty acids catabolism ATP amount after a total oxidation of palmitate (C16:0): 2n (number of C)/n=C/2 n-1 tours/cycles n Acetyl-CoA n-1 NADH n-1 FADH2 16  Fatty acids catabolism Beta oxidation of fatty acids (2n+1):  Propionyl CoA as final product Succinyl-CoA (Krebs cycle) 17  Fatty acids catabolism Beta oxidation of mono-unsaturated fatty acids: 18  Fatty acids catabolism Beta oxidation of poly-unsaturated fatty acids: 19 Ketone bodies 20 Ketone bodies 21  Ketone bodies Ketone bodies are:  water soluble molecules  alternative form of energy of the body (brain/kidney/muscles/heart)  Produced in the liver in the mitochondria  Their hydrolysis produces ATP  Red blood cells are strictly glucodependent  Their over production leads to metabolic acidosis  Regulated (ketogenisis/ketolysis) 22  Ketone bodies Ketone bodies are:  Synthetized:  Non untreated/uncontrolled Diabetes  Fasting state  High protein diet  Lower the pH of blood (metabolic acidocis)  Excreted in urine by kidney  Exhaled as acetone by lungs 23 Ketone bodies 24  Ketone bodies Acetoacetate = 22 to 23 molécules d’ATP Beta-hydoxybutyrate = 25 to 26 molécules d’ATP 25  Fatty acids anabolism Synthetized in the cytoplasm of: Activation phase: 26  Fatty acids anabolism WAKIL helix Fatty acids synthase 27 Fatty acids anabolism 1 : condensation 2 : reduction 3 : dehydratation 4 : reduction Fatty acids synthase 28  Fatty acids anabolism Fatty acids with more than 16 Carbons: mitochondria using elongases Long and unsaturated fatty acids: smooth endoplasmic reticulum using elongases and desaturases Essential fatty acids: omega 3 and 6 29  Triglycerides anabolism TG substrates synthesis:  Acyl-CoA  Monoglyceride  Digly  Glycerol-P TG synthase Common pathway to phospholipids synthesis Occurs in the liver, fatty tissues and intestine 30 Triglycerides anabolism 31  Phospholipids anabolism Phospholipids substrates synthesis:  Phosphatidic acid (from TG pathway)  ALcohols 32  Phospholipids anabolism Many synthesis substrates Several reactions Statins 43 steps Key enzyme: HMG-CoA reductatse Consumes ATP and NADPH Statins inhibits HMG-COA reductase 33  Cholesterol regulation Statins inhibits HMG-COA reductase Hormone regulation : 34  Cholesterol derivatives Bile acids = bile salts  Detergents or surfactants  Amphipathic or amphiphilic compounds  Derivate from cholesterol  Liver/Colon by bacteria  Gallbladder/bile duct  Lipid digestion, cholesterol solubilization and antibiotic action  Primary, secondary and tertiary bile salts  Primary bile salts are conjugated to taurine and glycine 35  Cholesterol derivatives Bile acids = bile salts 36  Cholesterol derivatives Vitamin D 37  Cholesterol derivatives Steroids hormones 38 THANK YOU ! 39 THANK YOU ! 39 THANK YOU ! 39 THANK YOU ! 39 THANK YOU ! 39