Lipid Metabolism through the intestines Utilization of dietary lipids requires that they first be absorbed The process of Digestion and Absorption o Solubilization emulsification by Bile salts o Degradation pancreatic lipases lipase and phospholipase A2 are enzymes that digest lipids they break the lipids apart o Absorption by the intestines The pieces of the lipids are surrounded by bile o Resynthesis salts to be absorbed in the intestines Once their inside the enterocyte the triglydercides cholesterol and phospholipids reform o Formation of lipoprotein complexes complexes of lipid and protein called chylomicrons Chylomicrons are lipoproteins made from o Hydrolysis back to protein and free fatty acids exogenous lipids and transport them to tissues through the lymph lipoprotein lipase free fatty acids and glycerol absorbed into adipose tissue Glycerol returns to the liver fatty acids are enzymes that hydrolyzes TG to Fatty Acid sources o The primary source of fatty acids for oxidation are dietary and mobilization from cellular stores Fatty acids are stored in the form of triacylglycerols primarily within adipocytes of adipose tissue In response to energy demands the fatty acids of stored triacylglycerols can be mobilized for use by peripheral tissues o The release of fatty acids or metabolic energy from triacylglycerols in adipocytes is controlled by activating the hormone hormone sensitive lipase stimulate this o Glucagon epinephrine or b corticotropin in adipocytes o this process just explains how enzymes break free fatty acids from triacylglcerols that are stored in adipocytes to be used for energy and its controlled by hormones o The process figure 21 3 A hormone binds to a receptor on the plasma membrane of the adipocyte This hormone binding activates adenylate cyclase which leads to production of active protein kinase A PKA cAMP dependent protein kinase sensitive lipase atoms 1 or 3 of triacylglycerols either hormone sensitive lipase or the non inducible enzyme monoacylglycerol lipase PKA phosphorlates and activates hormone This enzyme hydrolyzes fatty acids from carbon The resulting diaclyglycerols are substances for o The net result of the action of these enzymes is 3 free fatty acids and one glycerol The free fatty acids diffuse from adipose cells combine with albumin in the blood and transported to other tissues where they passively diffuse into cells o How does insulin affect this In contrast to the hormonal activation of adenylate cyclase and hormone sensitive lipase in adipocytes the transportation of fat from adipose tissues is inhibited by numerous stimuli The most significant inhibition is that exerted upon adenylate cyclase by insulin When an individual is well fed state insulin released from the pancreas prevents the inappropriate mobilization of stored fat Instead any excess fat and carbohydrates that were consumed are placed in the triacylglycerol pool within adipose tissue more fat Insulin doesn t let triacylglycerol be broken down for energy instead the extra fat and carbs that we eat are added to the adipose tissue as fat Activation Step for B Oxidation o Once we get free fatty acids chain from the adipocytes they go through B Oxidation which is the break down of long chain fatty acids for energy before being oxidized in the mitochondria called acyl CoA synthetase or thiokinase o Fatty acids must first be activated in the cytoplasm o Activation is catalyzed by fatty acyl CoA ligase also o This step requires 2 ATP and is located in the cytosol o B Oxidation occurs in the mitochondria However Fatty Acyl CoA cant travel into the mitochondria so it needs to be converted to Acyl Carnitine intermediate with the help of carnitine acyltransferase I an enzyme that resides in the outer mitochondrial membrane from acyl CoA and carnitine o The Acyl Carnitine molecule then is transported into the mitochondria where carnitine acyltransferase II converts it back into Fatty Acyl CoA B Oxidation section 1 3 of video o The whole cycle requires 4 reactions o 1 Acyl CoA dehydrogenase catalyzes oxidation of acyl group to form enoyl CoA o 2 Enoyl CoA hydratase hydrates adds water across the double bond of the unsaturated acyl CoA to make B hydroxyacyl CoA o 3 A second oxidation reaction is catalyzed by B o 4 Thiolase cleaves two carbon atoms from the B hydroxyacyl dehydrogenase an NAD dependent enzyme The product is B ketoacyl CoA ketoacyl CoA the product is acetyl CoA the 2 cleaved carbons and acyl CoA which is now 2 carbon shorter A second CoA molecule is needed to form the new thioester bond in the smaller acyl CoA molecule This molecule then goes through the B Oxidation again section 4 5 of Energy Yield from Oxidation of Fatty Acids video o The process of fatty acid oxidation is termed B oxidation since it occurs through the sequential removal of 2 carbon units by oxidation at the b carbon position of fatty acyl CoA molecule 1 NADH 3 ATP 1 FADH 2 ATP o Each round of B Oxidation produces Total ATP for each round of B Oxidation is 5 o the acetyl CoA the end product of B Oxidation then enters the Krebs Cycle where it is further oxidized to CO2 with the conmitant generation of ATP 1 Acetyl CoA 3 NADH 9 ATP 1 FADH 2 ATP 1 ATP Total ATP for each acetyl CoA is 12 o the NADH and FADH generated during the fat oxidation and acetyl CoA oxidation in the TCA cycle then can enter the respiratory pathway for the production of ATP o Example Fatty Acid 16C 7 rounds x 5 ATP 35 ATP 8 acetyl CoA x 12 ATP 96 ATP activation step 2 ATP TOTAL 129 ATP o the oxidation of fatty acids yield significantly more energy per carbon atom than does the oxidation of carbohydrates o the net result of the oxidation of one mole of oleic acid 18 C fatty acid will be 146 moles of ATP 2 mole equivalents are used during the activation of the fatty acid number of glucose carbon atoms o Catabolism of Odd Carbon Fatty Acids compared with 114 ATP from an equivalent section 7 Odd numebered fatty acids also undergo B Oxidation but the last cycle produces one molecule of propionyl CoA pathway to convert it to succinyl CoA which then enters the kreb cycle In this pathway propionyl CoA is first carboxylated to methylmalonyl CoA with the help of propionyl CoA carboxylase which then undergoes rearrangement to form succinyl CoA The propionyl CoA undergoes an enzymatic Acids section 6 o B Oxidation of Monounsaturated Polyunsaturated Fatty The ocnversion of a MUSFA to acetyl CoA requires a cis trans isomerization B Oxidation can