Fatty Acid Oxidation - Almaaqal University PDF

Almaaqal University Fatty Acid oxidation Dr/ Wael Sobhy Darwish Biochemistry PhD  Fatty Acid oxidation Fatty Acid oxidation Major Pathway...

Almaaqal University Fatty Acid oxidation Dr/ Wael Sobhy Darwish Biochemistry PhD  Fatty Acid oxidation Fatty Acid oxidation Major Pathway Minor Pathway β-oxidation α-oxidation ω-oxidation Fatty acid oxidation is a major source of cell ATP.  β-oxidation Pathway Site 1. Intracellular location: Mitochondria where the various enzymes for fatty acid oxidation are present close to the enzymes of the electron transport chain. 2. Organ location: a) Liver, kidney, heart and skeletal muscles. b) β-Oxidation never occur in brain, fatty acid can’t pass blood brain barriers and RBCs (no mitochondria). Oxidation of FAs occur at the β-carbon atom resulting in the elimination of the two terminal carbon atoms as acetyl CoA leaving fatty acyl CoA which has two carbon atoms less than the original fatty acid.  Steps of β-oxidation of Fatty Acids Activation of fatty Transport of fatty β-oxidation acids acids into (Mitochondrial (Cytosol) mitochondria matrix) 1- Activation of Fatty Acids. In the cytosol by enzyme thiokinase 2 ATP 2- Transport of Acyl-CoA from Cytosol into Mitochondria by Carnitine Shuttle: Function of Carnitine: It transports long chain acyl CoA inside the mitochondrial matrix where enzymes for β-oxidation are present.  β-oxidation has 4 steps: 1-Dehydrogenation (FAD-dependent) 2- Hydration 3-Dehydrogenation (NAD-dependent) 4-Cleavage (Remove 2C as acetyl CoA)  Calculations Carbons in Fatty Acetyl CoA β-oxidation cycles Acid C/2 (C/2) -1 12 6 5 14 7 6 16 8 7 18 9 8 Note: In each round of β-oxidation one molecule of FADH2 and one molecule of NADH+H+ are produced which generates 2 and 3 ATP molecules, respectively  Example: Energy of palmitoyl ~Co A (16 C) oxidation Number of cycles= n/2 -1 = 7 cycles Number of acetyl ~Co A = n/2 =8  So, 7 NADH, each provide 3 ATP when oxidized in the ETC 7X3=21 ATP  7 FADH2 each provide 2 ATP when oxidized in the ETC 7x 2=14 ATP  8 acetyl ~Co A , each provides 12 ATP by the TCA cycle 8x12= 96 ATP So total So total energy energy yield yield of of oxidation oxidation of of palmitoyl palmitoyl ~Co ~Co A A== 21 21 ++ 14 14 ++ 96 96 == 131 131 ATP ATP As 2 molecules of ATP are used in the activation of a molecule of fatty acid Therefore, there is a net yield of 129 molecules of ATP  IMPORTANCE (FUNCTIONS) OF β -OXIDATION: 1. Energy production e.g. palmitic acid produces 129 ATP. 2. Production of acetyl CoA: which enter in many pathways. 3. Ketone bodies formation: Acetoacetyl CoA is the last 4 carbons product in the course of β-oxidation of even numbered fatty acids. It may be converted into acetoacetate; one of ketone bodies.  Oxidation of Unsaturated Fatty Acid Slightly more complicated Requires additional enzymes Oxidation of unsaturated FAs produce less energy than that of saturated FAs (because they are less highly reduced, therefore, fewer reducing equivalents can be produced from these structures)  Oxidation of Odd Numbered Fatty Acid Requires three additional extra reactions. Odd numbered lipids are present in plants and marine organisms. Fatty acids with odd number of carbon atoms are also oxidized by the same process β-oxidation as even chain FAs, removing 2 carbons as acetyl CoA in each round of the oxidative process BUT the final round of β-oxidation of a fatty acid with an odd number of C atoms yields acetyl-CoA & propionyl-CoA (3C).  α-Oxidation Pathway This type of oxidation occurs in α- position and characterized by: 1. It is a mechanism mainly for oxidation of branched chain fatty acid, which are methylated at β-position. 2. It is specific for oxidation of Phytanic acid, present in plant foodstuffs. 3. It is minor pathway for fatty acid oxidation, occurs mainly in brain and nervous tissues. In α-oxidation, there is one carbon atom removed at a time from α position It does not require CoASH and does not generate high energy phosphate. REFSUM’S DISEASE: Def: inherited deficiency of enzymes responsible for α-oxidation of Phytanic acid. Manifestation: accumulation of Phytanic acid in nervous tissue and produce nervous damage e.g. deafness and blindness  ω-Oxidation Pathway ω-oxidation is a minor pathway and occurs in the endoplasmic reticulum of many tissues rather than the mitochondria, the site of β- oxidation. This process occurs primarily with medium chain FAs of adipose tissue which are mobilized to the liver under conditions of ketosis.