Oxidation of Fatty Acid

OXIDATION OF FATTY ACID / B-OXIΡΑΤΙΟΝ m INTRODUCTION: →Fatty acids are a class of long hydrocarbon chains and group. compounds containing a terminal carboxy) they are represented single bonds they if they they have in a chain of only are known as saturated and one or more arce Unsaturated fatty acids. double bond they Fatty acids are stored in biological system as fat cerides and lipase enzyme breaks it into and glycenols. fatty acids →Patty acids have two may'ure physiological roles, firstly as ane building blocks of phospholipids and glycolipids which are the important component of biological membrane and secondly they are fuel molecules Energy Stone of fatty acids: fatty acids are The complete highly Stories of metabolic energ energy.. oxidation of fatty acid yield a kcal/gom. In contrast with about ukcal/gm for carbohydrate and protein. oxidation of fatty acids : →Generally fatty acid carbon atoms are numberred starting at carboxyl terminous as following. 3 -(CH2)-CH₂CH₂- خط cacbon atom, al 22 3 respectively. ane reffered as 22B B-oxidation: In 1904 Freantz knoop made a crítical contribution to explain the fatty acid oxidation from his experiment he deduced that fatty acids by oxidation of the B-carbon. ane degraded → According to him duning B-oxidation fatty acid ane oxidised by successive loss of can bon fragments 2. Canbon Here the B-carbon of fatty acid is oxidized to yield a to form B-ketoacid. which then undergoes cleavage a 2-carbon fragment acetic acid, and thus original fatty acid chain shontere by 2- carbon a toms. CH3 CH3 (CHEM (+) 14 (+3 (+2) + Coo H Aceticid COOH (Stearicand) (Reto acid) Pal matic acid. →Fure there Albent Lehningere suggestest that oxidation of fatty acid in Liver yield active 2-carbon freagments that enter the citric acid cycle. Site of B-oxidation: →B-oxidation takes place in the Mitochondria of liver cell fatty acids are activated at outen Mitochondrial Membrane and they ane oxidized in the matrix of Mitochondria. Entrrance of fatty acid fiuto Mitochondria : Long chained fatty acid in to cytoplasm cann't Pax Pass through the Mitochondrial membrane They undergoes a series of 3. enzymatic reactions. to entere the mitochondrial matrix where finally It is oxidized. Step-1: Priore to entreance of fatty acid into Mitochondria the fatty acid is activated at ailen membrane Mitochondria. →Paul Bereg showed that activation of fatty acid occures in two Steps →Firest the fatty acid react with ATP to form Acyladenylate Here the cool group of fatty acid in linked to AMP → in the second step sulphohydroxyl group of con attacks the acyl adenylate to form acyl con and AMP-The enzyme catalyse the reaction is Acyl-CoA Synthetase. R-C +ATP R-CLOH R-C-AMP Acyladenylate + PP Pyrophosphate 3) R--AMP + HS-COA Synthetase R-2-S-COA+AMP Acyl CoA. Step-1: The long chain fatty acid cann't enter into the Ennen Mitochondrial Membrane →The activated long chain fatty acid is cannied across the innere membrane carnitine, by a cannier The acylgroup is transferined to -011 group of carnitine to form -fatty acyl carnitine in the presence of carinitine acyl transferase -I 1 Now the fatty acyl carnitine inner membrane. can diffuse across the R-C-S-COA+ carnitine HS-COA + Fatty acyl carnitine. Step-Ⅲ: transferase →In this step the fatty acyl carnitine aftere entreance to the matrix fatty acyl group is enzymatically transferred from carnitine The treansifer reaction is catalysed by enzyme camnitine acyl transferase - I in Fatty acyl carnitine + COA-SH Anans-temare Fatty -S-COA + carnitine The fatty acyl CoA is now ready fore oxidation of its fatty acid component by a Set of Specific enzyme in the matrix. Fatty acid oxidation in Matrix: on the matrix fatty acid is oxidised in two majon Stages. In the first stage the fatty acid Undergoes oxidative removal of successive 2-canbon Units Starting from cool end of the fatty acid chain. Thus a 16- can bon fatty acid called palmitic acid Undergoes seven passes. Through a set of enzymes each pass chopping off a 2-carbon Units as acetyl.con. In the 2nd stage the acetyl CoA ane oxidized to Co2 and H2o ria citric acid cycle In the Matrix Firest stage of oxidation: In the firest stage of oxidation 4-enzymes catalyze the reaction in following 4-steps. Step-1: (Dehydrogenation step) →After entry of the Satuaated fatty acyl col into the matrix it undergoes enzymatic dehydrogenation at the of and B carbon atoms to forem double bond in the carbon chain. →The enzymatic reaction yields a transenog!. COA from fatty acid-CoA an Unsaturated Product.. →The reaction is catalysed by enzyme acyl- COA dehydrogenase. The hydrogen accepton is FAD. الا R-CH2-CH-CH2-C-S-COA dehydrogenase, (fatty acyl CoA) PAD PADT R-CH2-CC-C-S-COA H (Treans enoyl CoA) step-1: (Hydration step) on the 2nd step watere Molecule adds to the double bond of the transenoyl CoA to form the B-Hydroxyl acyl -S-COA catalysed by enoyl CoA- ydratase hydratase Treans enoyl COA +120 Enoyl CoA Hydnatase B-Hydno- xyl acyl-s-cot step-ilt: C second behydrogenation step) on the sind step hydroxyl acyl cot cot te dehydro catalyse catalyse the reaction is drogenase Hydroxyacyl CoA COA-dehy Hene NAD to the hydrogen receptor." genated to form 3- Keto acyl CoA. The enzyme Hydroxylacy! S-COA +NAD+ Dehydragenere 3-ketoacy! S-COA+NADH+HT Step-1: (cleavage step) In this step enzyme acetyl CoA-treansferase ore thiolase promotes reaction of 3-keto acyls-Cot with a molecule of free COA-SH to split of the carboxyl terminal 2-carbon fragment of the original fatty acid as other product. acetyl CoA. leaving the 7 This reaction is also called as thiolysis. R-CH2-CH2-S-COA (keto acyl-s-CoA) COA-SH Thio lase R-Cth-2-S-COA (Shortened FIA Chain) + H₂--S-COA (Acetyl con) * ATP out put in firest stage of B-oxidation! In the first stage of Ro-oxidation along with. Splitting of two patry of one molerwe of Acetyl cot successively hydrogen atoms are released in dehydrogenation steps. Taking the example of palmitic acid a 16-e. fatty add the following overall balance reaction can be made aftere removal of successively. Palmistyl S-COA +7 COA-S11 +7 FAD +7 NAD +7 H20 8 acepy.co A +7 FADt+7 NADH +7H. →Thus each molecule of PADH, formed 2A4TP. Similarly Each NADHtHt form 3 ATP in Electron transporting system per molecule of So 7x5 ATP of oxidation. So 5-ATP are formed acetyl cot removed in each step. = 35 ATP removed in 4st stage b) Second stage of B-Oxidation! → on the 2nd stage of B-oxidation acetyl CoA is finally oxidised via citric acid cycle on matrix and produce eas and H20 with production Of 96 ATP. The following equation represents the of ATP for the 2nd Stage of 16. palmitic acid. 8 Acetyl CoA +1602 + 96 ADP +96 P3 - 800A-SH+ 96 ATP + 104+120+16102. →There fore the gain of ATP after oxidation of one Molecule of AP palmitic. acid is 96+35= activation of Consumed So 131 ATP But during Fatty acid 2 ATP has met gain - net net is 129 ATP 131-2-