Lipid Metabolism Lesson 19 PDF

LIPID METABOLISM Lesson 19 LIPID METABOLISM • Structure, properties and classification of lipids • Digestion and absorption of lipids. Transport of lipids in the blood. • Lipid storage and removal. Energy yield. • Role of carnitine in the metabolism of fatty acids BIOLOGICAL FUNCTIONS A chemical...

LIPID METABOLISM Lesson 19 LIPID METABOLISM • Structure, properties and classification of lipids • Digestion and absorption of lipids. Transport of lipids in the blood. • Lipid storage and removal. Energy yield. • Role of carnitine in the metabolism of fatty acids BIOLOGICAL FUNCTIONS A chemically diverse group of compounds, the common and defining feature of which is their insolubility in water  In consequence: Diverse biological functions Lipids are hydrophobic CLASSIFICATION OF LIPIDS- BASED ON ITS STRUCTURE Aclyglycerides Terpenes Sterol lipids Eicosanoids Cannot be divided into simple structural units COMPLEX SIMPLE Fatty acids Phosphoaclyglicerides Sphingolipids Waxes Can be divided into several structural units FATTY ACIDS • Carboxylic acids (-COOH) with hydrocarbon chains ranging from 4 to 36 carbons long • Stored forms of energy • Poor solubility of fatty acids in water • Classification according to hydrocarbon chains: Saturated FA  contains no double bonds Insaturated FA contains one or more double bonds Saturated FA Insaturated FA ACLYGLYCERIDES • Composed of 1, 2 or 3 fatty acids linked with a single glycerol • Nonpolar, hydrophobic molecules  insoluble in water TYPES Monoaclyglycerides Diaclyglycerides Triaclyglycerides Principal stored energy Lipid droplets in Adipose tissue STEROLS-CHOLESTEROL • Structural lipid present in the cell membranes • Amphipathic molecule Polar head group  -OH group Nonpolar hydrocarbon body the steroid nucleus and side chain • Precursor for a variety of products with specific biological activities: Steroid hormones  Estogenes, testosterone, progesterone, cortisol Bile acids  detergents in the intestine, emulsifying dietary fats to make them more readily accessible to digestive lipases Vitamin D DIGESTION AND ABSORPTION OF LIPIDS DIGESTION AND ABSORPTION OF LIPIDS • Triacylglycerols from the diet form lipid droplets in the stomach. Bile salts, secreted by the gall bladder, insert into the lipid droplets, rendering them more accessible to digestion by lipases. • Lipases, secreted by the pancreas, convert the triacylglycerols into 2 fatty acids and monoacylglycerol. • The digestion products are carried as micelles to the intestinal epithelium cells for absorption. • In the intestine, triacylglycerols are reformed from free fatty acids and monoacylglycerol and packaged into lipoprotein particles called chylomicrons. • The chylomicrons enter the blood so that the triacylglycerols can be absorbed by tissues. TRANSPORT OF LIPIDS IN THE BLOOD How can lipids be transported in the blood if they are insoluble in water? Lipoproteins: Macromolecular complexes of specific carrier proteins and various combinations of lipids • The protein(s) serve to solubilize the lipids and to direct the particles to specific targets. • Depending on the kind of lipid that form part of it and the direction of the transport (from which tissue to which tissue it is transported) , there are different types Apoprotein: The protein component of a lipoprotein. LIPOPROTEINS Chylomicrons Very-low-density lipoprotein (VLDL) Low-density lipoprotein (LDL) High-density lipoprotein (HDL) Carry dietary lipids (TG) from the intestine to liver where they will be consumed or stored as fuel Transporte TG synthesized in the liver to other tissues (mainly muscle and adipose tissue) for storage or to supply energy Further removal of TG from VLDL produces LDL. Carry cholesterol from the liver to other tissues Reverse cholesterol transport Pick up cholesterol from extrahepatic tissues and returns it to the liver TRANSPORT OF LIPIDS IN THE BLOOD LIPID STORAGE • When the diet contains more fatty acids than are needed immediately for fuel • Triacylglycerols are stored in adipocytes (cells from the adipose tissue) in lipid droplets • When there is a need for metabolic energy, triacylglycerols stored in adipose tissue are mobilized (brought out of storage) and transported to tissues in which fatty acids can be oxidized for energy production. LIPID REMOVAL The fatty acids stored in the form of triacylglycerols in the adipose tissue are converted into energy in three stages: 1. Mobilization of triacylglycerols stored in adipose tissue 2. Activation of the fatty acids and transport into the mitochondria for oxidation. L-carnitine is required. 3. Degradation of the fatty acids to acetyl CoA for processing by the citric acid cycle. LIPID REMOVAL 1. MOBILIZATION OF TRIACYLGLYCEROLS STORED IN ADIPOSE TISSUE • Degradation of TAG to release fatty acids and glycerol (LIPOLYSIS) into the blood for transport to energy-requiring tissues • Stimulated by:  Epinephrine Fight-or-flight situation  Glucagon  Fasting • Triacylglycerols are hydrolyzed by hormonesensitive lipase (HSL) to 3 fatty acids and 1 glycerol molecule • Fatty acids and glycerol are delivered to the bloodstream and reach different tissues where there is an energy demand (except the brain). LIPID REMOVAL 2. ACTIVATION OF THE FATTY ACIDS AND TRANSPORT INTO THE MITOCHONDRIA FOR OXIDATION • Fatty acids must be activated by a fatty acyl–CoA synthetase  Fatty acyl–CoA • Activated fatty acids entry into mitochondria via the acyl-carnitine/carnitine transporter LIPID REMOVAL 3. DEGRADATION OF THE FATTY ACIDS TO ACETYL COA FOR PROCESSING BY THE CITRIC ACID CYCLE  β-OXIDATION • It consists of several oxidation rounds, and in each one the fatty acid is shortened in two carbon atoms as Acetyl CoA is released • Acetyl CoA is directed to the CAC. • Also in each round coenzymes NADH and FADH2 are produced, and directed to the ETC. With this process, a huge amount of energy is produced if we compare it with the energy produced from glucose degradation, but oxygen is always required. (aprox. 130 ATP from Fatty acids vs 38 from glucose) FATTY ACIDS SYNTHESIS • Synthesis of FA from Acetyl-CoA derived from the degradation of glucose or amino acids • Location  Cytosol • Organ  Liver • Enzyme  Fatty acid synthase • Consists of several rounds and in each one the fatty acid chain grows in two carbon atoms. Reverse pathway to β-oxidation with different location and different enzymes OVERALL REGULATION OF LIPID METABOLISM FASTING AND EXERCISE AFTER A MEAL AND RESTING Glucagon and Epinephrine Insulin Activation of lipolysis and β-oxidation Activation of fatty acid synthesis Inhibition of fatty acid synthesis OVERALL REGULATION OF LIPID METABOLISM Carbohydrate-rich diets promote fatty acid synthesis The excess Acetyl CoA formed from glucose is actively transformed in triacylglycerides