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    Add as Friendoxidation of fatty acids

    by: Ravi

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    1 : ß- Oxidation ? it is defined as oxidation of fatty acids on ß-carbon atom. ? this results in sequential removal of two carbon fragment, acetyl-CoA. ? The ß-oxidation of fatty acids involve three stages: Activation of fatty acids occurring in cytosol transport of fatty acids into mitochondria ß-oxidation proper in mitochondrial matrix. ? brain, erythrocytes and adrenal medulla cannot utilize fatty acids for energy requirement. Activation of fatty acids occurring in cytosol: ? fatty acids are activated to acyl CoA by Thiokinase or acyl CoA synthetases.
    2 : ? fatty acids reacts with ATP to form acyladenylate which combines with coenzyme A to produce Acyl CoA. ? In this activation two high energy phosphates are utilized & ATP is converted into Inorganic pyrophosphate by inorganic phosphatase to inorganic phosphate. ? this immediate elimination of PPi makes the reaction irreversible. ? 2. transport of acyl CoA into mitochondria: ? inner mitochondrial membrane is impermeable to fatty acids. ? a specialized carnitine carrier system or carnitine shuttle operates the transport of fatty acids from cytosol to mitochondria by four steps.
    3 : ? step 1: acyl group of acyl CoA is transferred to carnitine / ß-hydroxy ?-trimethyl aminobutyrate which is catalysed by carnitine acyltransferase I. ? step 2: acyl carnitine is transported across membrane to mitochondrial matrix by specific carrier protein. ? step 3: carnitine acyl transferase II converts acyl carnitine to acyl CoA. ? Step 4: carnitine released returns to cytosol for reuse. ? coenzyme A used for activation is different from the one that finally combines with fatty acids in mitochondria to form acyl CoA. ? Therefore cell has two separate pools (cytosol & mitochondria) of coenzyme A & Carnitine acyl transferase I is inhibited by malonyl CoA.
    4 : ? 3. ß- Oxidation proper in mitochondrial matrix: ? 1.oxidation: acyl CoA undergo dehydration by FAD –dependent flavoenzyme called acyl CoA dehydrogenase. ? a double bond is formed between a & ß carbons. ? 2. hydration: enoyl CoA hydratase brings hydration of double bond to form ß-hydroxyacyl CoA. ? 3. Oxidation: ß- hydroxyacyl CoA dehydrogenase catalyses second oxidation and generates NADH. ? The product formed is ß-ketoacyl CoA thiolase. ? 4. cleavage: it liberates two carbon fragment, acetyl CoA from Acyl CoA.
    5 : ? This occurs by thiolytic cleavage catalyzed by ß-ketoacyl CoA thiolase. ? the new acyl CoA containing two carbon less reenters ß-oxidation cycle. Overall reaction for each cycle of ß-oxidation: Cn Acyl CoA + fad + NAD+ + H2O + CoASH-------? C(n-2) Acyl CoA + Acetyl CoA + FADH2 + NADH + H+ Summary of ß-oxidation of Palmitoyl CoA: Palmitoyl CoA + 7 CoASH + 7 FAD + 7 NAD+ + 7H2O----? 8 Acetyl CoA + 7 FADH2 + 7 NADH + 7 H+ ? Acetyl CoA can enter TCA cycle and gets completely oxidized to carbon dioxide and water molecule.
    6 : Bioenergetics ? Palmitoyl CoA undergo 7 cycles of ß-oxidation to yield 8 Acetyl CoA. ? (Each time, ß-oxidation produces 5 ATP.) MECHANISM ATP Yield ß-oxidation – 7 cycles 7 FADH2 oxidized by ETC = 7*2 = 14 (each FADH2 gives 2 ATP) 7 NADH oxidized by ETC (each NADH liberate 3 ATP) = 7*3 = 21 From 8 Acetyl CoA (Oxidized by TCA Cycle & each = 8*12 = 96 Acetyl CoA provide 12 ATP)
    7 : _________ Total energy from one mole of palmitoyl CoA = 131 _____________ Energy utilized for activation of palmitoyl CoA = 2 ____________ Therefore net yield of oxidation of one molecule of palmitate ( 131-2) = 129 ATP _____________ Standard free energy of palmitate = 2340 Calories Energy yield by its oxidation(129ATP*7.3 Calories)=940 Calories Efficiency of energy conservation by fatty acid oxidation 940*100 / 2340 = 40 %

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