Lipid Metabolism Session 1 PDF

LIPID METABOLISM (Session 1) Rehana Omar School of Medicine Department of physiological sciences. [email protected]  Key components covered in Fatty acid metabolism ❖Digestion and absorption of fatty acids. ❖Fatty acid synthesis. ❖Fatty acid oxidation....

LIPID METABOLISM (Session 1) Rehana Omar School of Medicine Department of physiological sciences. [email protected]  Key components covered in Fatty acid metabolism ❖Digestion and absorption of fatty acids. ❖Fatty acid synthesis. ❖Fatty acid oxidation. ❖Regulation of fatty acid metabolism. ❖Ketogenesis. ❖Changes in fatty acid metabolism in uncontrolled diabetes and starvation. ❖The fate of cholesterol. At the end of this fatty acid metabolism component, each student should be able to; Explain why fatty acids are ideal for storage of energy over a long time. Describe changes in fatty acid metabolism associated with uncontrolled diabetes mellitus Illustrate the common origin of steroid hormones and how subtle differences in the position of functional groups results in functional diversity of the hormones Breakdown of carbohydrates, lipids and proteins Harper's Illustrated Biochemistry 26th ed  Introduction to fatty acid catabolism Fatty acid catabolism i.e break down of triacylglycerides to CO₂ and H₂0 to produce energy- process called β-oxidation Fatty acid oxidation can provide 80% of the energy needs of certain tissues e.g. the heart, liver and resting skeletal muscle Fatty acid chains get oxidized to water and CO₂ and their electrons pass on to the electron transport chain. Triacylglycerides are more highly reduced- i.e. they have many H atoms compared to carbohydrates The more reduced a compound is, the more energy it produces. Fats produce 2x the amount of energy from glucose  What makes lipids an ideal energy storage macromolecule? To answer this, we will start by comparing the structures of lipids and sugars; Amylose-a component of starch A triacyglycerol  Storage of fats No limit to storage of fats (in specialized fat cells called adipocytes) Hydrophobic therefore does NOT affect osmolarity of a cell Inert therefore not likely to react and harm the organism Storage of glycogen Stored in small amounts in liver (provides energy for up to 24 hrs) Polar, therefore solvated by water (2/3 of the weight)  Introduction to fatty acid catabolism Fatty substances are hydrophobic. Metabolic enzymes are water soluble. Digestion of fats requires features that help these fats be more susceptible to enzymes. Other mechanisms are required to transport these fats from the intestinal wall to cells. In the cells, still more mechanisms are needed to mobilize the stored fats and transport them into the mitochondrial matrix for β-oxidation.  Fatty Acid transport from dietary intake to cells Lehninger Principles of Biochemistry, Fourth Edition  Digestion of fats Bile salts (amphipathic molecules) interact with insoluble fat globules converting them into dispersed micelles made up of the bile and fat (increasing contact between molecules and enzymes). The liver makes bile from cholesterol and stores it in the gall bladder and releases it into the small intestine after consumption of a fatty meal. Bile acts like a detergent and this process of breaking fats is called emulsification  Digestion of Fats Water soluble intestinal lipases can now interact with the lipid/bile micelles and convert triacylglycerols into monoglycerols, diglycerols, glycerol and fatty acid chains These products diffuse from the intestine into the intestinal epithelial cells where they are re-formed creating triacylglycerols which are further packaged with cholesterol and specific proteins to create aggregates called chylomicrons. These specific proteins called apolipoproteins bind to this triglyceride, cholesterol complex to help transport these lipids between organs. Protein component of lipoprotein in chylomicrons serve as ligands which cell receptors recognize and aid movement of chylomicrons from intestinal lining to the blood via lymphatic system.  Structure of Chylomicrons Surface of chylomicron is made of phosphodiester head groups of triacylglycerides. The fatty acid chains face inwards away from the aqueous environment. They make up 80% of mass of chylomicron. Lipoproteins B-48, C-II and C-III serve as recognition sites for transport and metabolism Range from 100 to 500nm in diameter Lehninger Principles of Biochemistry, Fourth Edition  Digestion of Fats Apolipoprotein C-II activates lipoprotein lipase which hydrolyzes (breaks down) triacylglycerides to fatty acids and glycerol. These are then taken to target tissues depending on energy state of the body. In muscle: oxidized to release energy– e.g. when starving or doing demanding physical work In adipose tissue: stored as fat reserves (reconstituted as triacylglycerols)- e.g. in fully fed state (sufficient blood glucose levels) (Also stored in cells that synthesise steroid hormones like the ovaries, testes and adrenal cortex)..  Mobilization of stored fatty acid droplets Lehninger Principles of Biochemistry, Fifth Edition  Mobilization of fatty acids Lipid droplet is coated with perilipins- protect the lipid droplet from untimely lipid mobilization. Hormones signal release of fatty acids for use by metabolically active tissue e.g. skeletal muscle, heart and kidney Epinephrine and glucagon (response to low sugar levels). These hormones trigger formation of cyclic AMP by enzyme adenylyl cyclase (in the plasma membrane of adipocyte). In response to cAMP, perilipins (protein on stored fatty acid droplets get phosphorylated by cAMP dependent protein kinase A (PKA). Phosphorylated perilipins are now able to interact with hormone sensitive lipase within cytosol leading to hydrolysis of triglycerides to free fatty acids  Mobilization of fatty acids Action of lipase releases free fatty acids (FFAs) from the adipocyte into blood As many as 10 FFAs bind to serum albumin in the blood and thus get transported to heart, skeletal muscle and renal cortex. They are released from albumin and enter the cells of these organs via plasma membrane transporters This is a way of transporting an insoluble molecule within an aqueous medium (blood).  Transportation of fatty acids into the mitochondrial matrix This shuttle is an important rate-limiting/regulatory shuttle of β- oxidation. Lehninger Principles of Biochemistry, Fourth Edition  Transportation of fatty acids into mitochondria Enzymes of β-oxidation are found in the mitochondrial matrix. FFA with