Lipid Metabolism Lecture - 9 PDF

LIPID METABOLISM Lecture - 9 Digestion and Absorption of Lipids: Diet contains triglycerides, cholesterol, fatty acids phospholipids, etc. Major part of triglycerides are digested by pancreatic lipase. It acts on emulsified lipids only. The products are 3 fatty acids and one glycerol molecule...

LIPID METABOLISM Lecture - 9 Digestion and Absorption of Lipids: Diet contains triglycerides, cholesterol, fatty acids phospholipids, etc. Major part of triglycerides are digested by pancreatic lipase. It acts on emulsified lipids only. The products are 3 fatty acids and one glycerol molecule. Phospholipids are digested by phospholipases, secreted by pancreas and intestines. They are four in number, A1, A2, C and D. Cholesterol esterase hydrolyses cholesterol ester to free cholesterol and one fatty acid. Absorption of lipids: Primary products of lipid digestion are: free fatty acids, free cholesterol and glycerol. These together with bile salts form micelles (disc shaped structures). Mobilization of Fatty Acids from Adipocytes: When the energy supply from diet is limited, the body responds to this deficiency through hormonal signals transmitted to the adipose tissue by release of glucagon, epinephrine, or adrenocorticotropic hormone. The hormones bind to the plasma membranes of adipocyte cells and stimulate synthesis of cyclic AMP (cAMP). The cAMP activates a protein kinase that phosphorylates and in turn activates hormone-sensitive lipases. These lipases hydrolyze the triacylglycerols to produce fatty acid & glycerol. The free fatty acids (FFA) produced by lipolysis bind to albumin in the blood plasma and are transported to peripheral tissues. The glycerol is taken up by liver, and is either converted to glucose or to pyruvate. Transport of Fatty Acids to the Mitochondria: The fatty acids transported to the different cells must first be activated by reaction with Coenzyme A at the expense of ATP. The reaction is catalyzed by AcylCoA synthetase (thiokinase), found in the cytosol and mitochondria of cells. In order to undergo β-oxidation, the fatty acids must enter the mitochondria. This is done by a carrier protein known as Carnitine shuttle, which carries the fatty acid from cytosol to the mitochondria. In the mitochondria enzymes of oxidation of fatty acids are present and the process is known as β- CARNITINE SHUTTLE β-oxidation of Fatty Acids: The successive oxidative removal of two carbons in the form of acetyl–CoA beginning from the carboxyl end is called β-oxidation. It requires a set of enzymes. The oxidation is so called because the β carbon is oxidized during the oxidation process. It takes place in the mitochondria. 1. Acyl CoA dehydrogenase converts acyl CoA to acyl trans enoyl CoA 2. Hydratase converts it to 3-hydroxy acyl CoA. 3. Hydroxy acyl CoA dehydrogenase converts it to 3keto acyl CoA. 4. It is further converted to acetyl CoA by Thiolase. The cycle is repeated 7 times for palmitic acid (16 C) for complete oxidation. β-oxidation of Fatty Acids: Complete oxidation of fatty acid can be divided in to two stages. A. Formation of acetyl CoA. B. Oxidation of acetyl CoA to CO2, water via TCA cycle. Palmitoyl CoA + 7FAD + 7 NAD +7CoA = 8 Acetyl CoA+7FADH2 +7 NADH2. Energetics of I molecule of palimitic acid oxidation 7 FADH2 → 7 x 2 = 14 ATPs 7NADH2 → 7 x 3 = 21 ATPs 8 Acetyl CoA → 8 x 12 = 96 ATPs Total ATP produced from one molecule of palmitic acid is 131. Two ATPs are utilized, during activation of fatty acid. Therefore total gain of ATPs is 129.  Fatty acids are synthesized and degraded by different mechanisms:  Fatty acids are both oxidized to acetyl-CoA and synthesized from acetyl-CoA.  Although the staring material of one process is identical to the product of the other, fatty acid oxidation is not the simple reverse of fatty acid biosynthesis.  It is an entirely different process taking place in separate compartment of the cell.  This allows each process to be individually controlled. The Biosynthesis of Fatty Acids: Apart from diet, fatty acids can be synthesized in the body. Denovo synthesis of fatty acids take place in cytosol of liver, lactating mammary gland, adipose tissue and renal cortex. * Acetyl CoA is converted to Malonyl CoA by acetyl CoA carboxylase. * Malonyl CoA and acetyl CoA are attached to acyl carrier protein (ACP). *Malonyl ACP & acetyl ACP get condensed to ketoacyl ACP, by condensing enzyme. * Ketoacyl ACP gets reduced to hydroxyl acyl ACP by a reductase. It requires NADPHH. * It loses one molecule of water, forms 2- enoyl acyl ACP. Enzyme is dehydratase. * It undergoes reduction and forms Butyryl ACP. NADPHH and reductase are needed for the reaction. The formation of malonyl CoA is the committed step in fatty acid synthesis The main sources of NADPH for fatty acid synthesis are the pentose phosphate shunt. Regulation o Fatty Acid Synthesis: High carbohydrate diet increases synthesis. Palmitoyl CoA inhibits synthesis Fasting decreases fatty acid synthesis. Insulin stimulates fatty acid synthesis. Malonyl CoA, the product of fatty acid synthesis inhibits fatty acid oxidation by inhibiting the Carnitine shuttle. Thus fatty acid synthesis and oxidation can not go on simultaneously.  Few important points Diet contains lipids triglycerides, cholesterol, fatty acids phospholipids. Major part of triglycerides are digested by pancreatic lipase. Phospholipids are digested by phospholipases. Primary products of lipid digestion are: free fatty acids, free cholesterol and glycerol. Lipids together with bile salts form Carnitine shuttle carries the fatty acid from cytosol to the mitochondria. β-oxidation of Fatty Acids: The successive oxidative removal of two carbons in the form of acetyl–CoA beginning from the carboxyl end of a fatty acid is called β-oxidation. It is called β-oxidation because the β carbon is oxidized during the oxidation process. It takes place in the mitochondria. The cycle is repeated 7 times for palmitic acid (16 C) for complete oxidation.  Total ATP produced from one molecule of palmitic acid is 131. Two ATPs are utilized, during activation of fatty acid. Therefore total gain of ATPs is 129. Denovo synthesis of fatty acids take place in cytosol of liver, lactating mammary gland, adipose tissue and renal cortex. The main sources of NADPH for fatty acid synthesis are the pentose phosphate shunt.