CHAPTER 6. LIPID METABOLISM doc

INTERNATIONAL UNIVERSITY SCHOOL OF BIOTECHNOLOGY CHAPTER LIPID METABOLISM BIOCHEMISTRY Learning objectives Describe the metabolism of fatty acids The two main components of fatty acid metabolism are β oxidation and fatty acid synthesis Understand that the fatty-acid breakdown reactions of β oxidation result in the formation of reduced cofactors and acetyl-CoA molecules, which can be further catabolized to release free energy Understand that the oxidation of unsaturated, oddchain, and very-long-chain fatty acids requires additional enzymes, some of them in peroxisomes Understand how fatty acid synthesis resembles and differs from β oxidation Content Fatty acid activation Steps of β oxidation Energy yield of oxidation Oxidation of palmitate Unsaturated fatty acids Odd-chain fatty acids Content Very long-chain fatty acids Synthesis vs oxidation Steps of synthesis 10 Palmitate synthesis 11 Fatty acid synthases Conclusion Fatty Acid Metabolism LEARNING OBJECTIVES Fatty acids are an important energy source, for they yield over twice as much energy as an equal mass of carbohydrate or protein In humans, the primary dietary source of fatty acids is triacylglycerols This lecture will describe the metabolism of fatty acids The two main components of fatty acid metabolism are β oxidation and fatty acid synthesis Upon completion of this lecture, you will understand that the fatty-acid breakdown reactions of β oxidation result in the formation of reduced cofactors and acetylCoA molecules, which can be further catabolized to release free energy You will also understand that the oxidation of unsaturated, odd-chain, and very-long-chain fatty acids requires additional enzymes, some of them in peroxisomes In addition, you will understand how fatty acid synthesis resembles and differs from β oxidation FATTY ACID ACTIVATION Triacylglycerols are carried by lipoproteins to tissues, where hydrolysis releases their fatty acids from the glycerol backbone Fatty acids enter the cell and are activated in the cytosol This activation costs two ATP equivalents per fatty acid Most of the activated fatty acids are then shuttled into the mitochondria for β oxidation, but a small percentage are carried to the peroxisomes 10 STEPS OF SYNTHESIS Let’s take a closer look at the steps of fatty acid synthesis Before fatty acid synthesis can begin, an acetyl group must be transferred from coenzyme-A to an acyl carrier protein, called ACP The first step in the cycle adds a two-carbon unit to the growing fatty acid The two carbon atoms come from malonyl-CoA, which is produced from acetyl-CoA in a reaction requiring one molecule of ATP In the second step, NADPH is used to reduce the ketoacyl-ACP from step one In the third step, hydroxyacyl-ACP dehydrase catalyzes the removal of a water molecule from the hydroxyacyl-ACP produced in step two In the fourth step, a second NADPHdependent reduction converts the enoyl-ACP produced in step three to a fatty acyl-ACP two carbon atoms longer than the starting substrate In all, adding two carbon atoms to the fatty acid costs the cell one ATP and two NADPH molecules 50 51 52 53 54 55 PALMITATE SYNTHESIS Palmitate synthesis requires seven rounds of fatty acid synthesis In all, this costs the cell 49 ATP equivalents After the final round of fatty acid synthesis, a fatty acyl thioesterase catalyzes the removal of the fatty acid from the acyl carrier protein 56 57 58 59 FATTY ACID SYNTHASES 60 In bacteria and chloroplasts, fatty acid synthesis is carried out by several enzymes In mammals, the main reactions of fatty acid synthesis are carried out by one multifunctional enzyme made of two identical polypeptides Packaging several enzyme activities into one multifunctional protein like mammalian fatty acid synthase allows the enzymes to be synthesized and controlled in a coordinated fashion Also, the product of one reaction can quickly diffuse to the next active site 61 CONCLUSION Fatty acid metabolism is important to the function of many cells Note that in fatty acid synthesis, the chain is extended two carbon atoms at a time, at the expense of ATP In fatty acid oxidation, the chain is degraded two carbon atoms at a time, producing ATP The two pathways are regulated so that a cell can synthesize energy-storing fatty acids in times of plenty, and oxidize the fatty acids when the cell needs to generate ATP 62 63 Thank you for your kindly listening 64 ...Learning objectives Describe the metabolism of fatty acids The two main components of fatty acid metabolism are β oxidation and fatty acid synthesis Understand that... fatty acids is triacylglycerols This lecture will describe the metabolism of fatty acids The two main components of fatty acid metabolism are β oxidation and fatty acid synthesis Upon completion... oxidation Steps of synthesis 10 Palmitate synthesis 11 Fatty acid synthases Conclusion Fatty Acid Metabolism LEARNING OBJECTIVES Fatty acids are an important energy source, for they yield over twice