Lipid Metabolism PDF

CHAPTER-IV LIPID METABOLISM BETA-OXIDATION Beta-oxidation is the process by which fatty acids, in the form of acyl-CoA molecules, are broken down in mitochondria and/or peroxisomes to generate acetyl-CoA, the entry molecule for the citric acid cycle. The beta...

CHAPTER-IV LIPID METABOLISM BETA-OXIDATION Beta-oxidation is the process by which fatty acids, in the form of acyl-CoA molecules, are broken down in mitochondria and/or peroxisomes to generate acetyl-CoA, the entry molecule for the citric acid cycle. The beta oxidation of fatty acids involve three stages: 1. Activation of fatty acids in the cytosol 2. Transport of activated fatty acids into mitochondria (carnitine shuttle) 3. Beta oxidation proper in the mitochondrial matrix Fatty acids are oxidized by most of the tissues in the body. However, some tissues such as the adrenal medulla do not use fatty acids for their energy requirements and instead use carbohydrates. Energy yield The ATP yield for every oxidation cycle is 14 ATP (according to the P/O ratio), broken down as follows: Source ATP Total 1 FADH2 x 1.5 ATP = 1.5 ATP (some sources say 2 ATP)[citation needed] 1 NADH x 2.5 ATP = 2.5 ATP (some sources say 3 ATP) 1 acetyl CoA x 10 ATP = 10 ATP (some sources say 12 ATP) TOTAL = 14 ATP For an even-numbered saturated fat (C2n), n - 1 oxidations are necessary, and the final process yields an additional acetyl CoA. In addition, two equivalents of ATP are lost during the activation of the fatty acid. Therefore, the total ATP yield can be stated as: (n - 1) * 14 + 10 - 2 = total ATP For instance, the ATP yield of palmitate (C16, n = 8) is: (8 - 1) * 14 + 10 - 2 = 106 ATP Represented in table form: Source ATP Total 7 FADH2 x 1.5 ATP = 10.5 ATP 7 NADH x 2.5 ATP = 17.5 ATP 8 acetyl CoA x 10 ATP = 80 ATP Activation = -2 ATP NET = 106 ATP For sources that use the larger ATP production numbers described above, the total would be 129 ATP ={(8-1)*17+12-2} equivalents per palmitate. Beta-oxidation of unsaturated fatty acids changes the ATP yield due to the requirement of two possible additional enzymes. Ketogenesis Ketogenesis is the process by which ketone bodies are produced as a result of fatty acid breakdown. Types of ketone bodies The three ketone bodies are: Acetoacetate, which, if not oxidized to form usable energy, is the source of the two other ketone bodies below Acetone, which, unlike free fatty acids, can be used by the brain for energy. Acetone is generated through the decarboxylation of acetoacetate which may occur spontaneously or through the enzyme acetoacetate decarboxylase. β-hydroxybutyrate, which is not, in the technical sense, a ketone according to IUPAC nomenclature. It is generated through the action of the enzyme D-β-hydroxybutyrate dehydrogenase on acetoacetate. Ketogeenesis pathw way. Ketolysis Each of these compo ounds is syntthesized from m acetyl-CoA A moleculess hesis of Fattty Acids BioSynth Fatty aciid synthesiss is the creattion of fatty acids from acetyl-CoA a and malonyll-CoA precuursors through action a of en nzymes called fatty acid synthases. It I is an impoortant part of o the lipogeenesis process, which - togeether with gllycolysis - sttands behindd creating faats from bloood sugar in living l organism ms. Much likke β-oxidatioon, straight-chain fatty acid a synthessis occurs viia the six reecurring reacctions shown beelow, until th he 16-carbonn palmitic accid is producced. The diaggrams presen nted show how h fatty accids are synnthesized in microorganiisms and lisst the enzymes found in Escherichia E coli. These reactions area performeed by fatty acid synthaase II (FASII), which in geeneral contaiin multiple enzymes e thatt act as one complex. FA ASII is preseent in prokaryootes, plants, fungi, f and paarasites, as well w as in miitochondria. In animaals, as well as a yeast and some fungi,, these samee reactions occur o on fattty acid synthhase I (FASI), a large dimeeric protein that t has all of the enzym matic activitties requiredd to create a fatty acid. FASI is less eff fficient than FASII; how wever, it allowws for the formation fo off more moleccules, includingg “medium-cchain” fatty acids via earrly chain term mination. Saturateed Straight-Chain Fattyy Acids Once a 16:0 1 carbon fatty acid has h been forrmed, it cann undergo a number of modification m ns, in particularr by fatty acid synthase III (FAS SIII), whichh uses 2 caarbon moleccules to elonngate preformeed fatty acidss. Regulatiion CoA is formeed into maloonyl-CoA by acetyl-CoA carboxylaase, at whichh point malonyl- Acetyl-C CoA is destined d to feed f into thhe fatty acid synthesis pathway. p Accetyl-CoA caarboxylase is i the point off regulation in saturated straight-cchain fatty acid syntheesis, and is subject to both phosphorrylation andd allosteric regulation. Regulation by phosphhorylation occurso mostly in mammals, while allosteric reguulation occurrs in most organisms. Allosteric controlc occuurs as feedbackk inhibition by b palmitoyyl-CoA and activation by b citrate. When W there are a high leveels of palmitoyyl-CoA, the final producct of saturatted fatty acid synthesiss, it allosteriically inactiivates acetyl-CooA carboxylase to prevvent a buildd-up of fattyy acids in cells. c Citratee acts to acttivate acetyl-CoA carboxylase under high levels, because high levels indicate that there is enough acetyl-CoA to feed into the Krebs cycle and produce energy. K.ANITA PRIYADHARSHINI LECTURER DEPT.OF PHARMACEUTICAL CHEMISTRY SRM COLLEGE OF PHARMACY