ß-Oxidation of fatty acids

ß-Oxidation of fatty acids

    • In 1904, Franz Knoop made a critical contribution to the elucidation of the mechanism of fatty acid oxidation and demonstrated that most of the fatty acids are degraded by oxidation at the ß carbon.
    • ß Oxidation of fatty acids takes place in mitochondria. Fatty acids are activated before they enter into mitochondria for oxidation. Activation of fatty acids.
    • Fatty acids are converted into active intermediate in a reaction with ATP and coenzyme A. A thioester linkage between the carboxyl group of a fatty acid and the sulfhydryl group of coenzyme A is formed with the hydrolysis of ATP.
    • This activation reaction takes place on the outer mitochondrial membrane catalysed by acyl CoA synthetase.
    • Several acyl CoA synthetases each specific for fatty acids of different chain length are present in the membrane of mitochondria.

    Penetration of long chain fatty acids into mitochondria
    • Long chain acyl CoA molecules do not readily get into the inner mitochondrial membrane and are carried across the inner membrane by conjugating with carnitine (ß hydroxy trimethyl ammonium butyrate), a zwitterionic compound formed from lysine.
    • Activation of lower fatty acids and their oxidation within the mitochondria occur independently of carnitine, but long chain acyl CoA will become oxidised unless they form acylcarnitines.
    • The acyl CoA combines with carnitine in the presence of carnitine acyltransferase I, which is bound to the outer mitochondrial membrane.
    • Acylcarnitine is transported in, coupled with the transport out of one molecule of carnitine.
    • The acylcarnitine then reacts with coenzyme A catalyzed by carnitine palmitoyl transferase II, located on the inside of the inner membrane.
    • Acyl CoA is reformed in the mitochondrial matrix and carnitine is liberated

    Oxidation

    • A saturated acyl CoA is oxidised by a recurring sequence of four reactions.Oxidation in presence of FAD, hydration, oxidation in presence of NAD+, and thiolysis by CoASH.
    • In ß oxidation, 2 carbons are cleaved at a time from acyl CoA molecules, starting from the carboxyl end.
    • The chain is broken between the α-and ß-carbon atoms. The two carbon units formed are acetyl CoA.
    • The first reaction in ß oxidation of acyl CoA is the formation of trans Δ2- enoyl CoA or α, ß unsaturated acyl CoA in presence of acyl CoA dehydrogenase and the coenzyme, FAD.
    • The next step is the hydration of the double bond between C 2 and C 3 by enoyl CoA hydratase with the formation of ß hydroxy acyl CoA.
    • In the third step, the ß -hydroxy acyl CoA is dehydrogenated in the presence of ß-hydroxy acyl CoA dehydrogenase and NAD+ forming ß ketoacyl CoA. In the last step of ß oxidation, ß ketoacyl CoA reacts with coenzyme A in the presence of the enzyme, thiolase.
    • The products of this reaction are acetyl CoA and an acyl CoA containing two carbons less than the original acyl CoA molecule that underwent oxidation.
    • By the above steps of ß oxidation fatty acids are completely degraded to acetyl CoA units.
    • The acetyl CoA formed from fatty acids can be oxidised to carbon dioxide and water via citric acid cycle.

    Energetics of ß oxidation

    • The energetics or the energy conserved in terms of ATP by oxidation of a molecule of palmitic acid is given below:
    • Palmitic acid (16 carbons) undergoes ß-oxidation forming eight molecules of acetyl CoA by undergoing seven ß oxidation spirals.
    • When one cycle of ß oxidation takes place, one molecule of FADH2, one molecule of NADH and one molecule of acetyl CoA are produced.
    • Electrons from these reducing equivalents (FADH2 and NADH) are transported through the respiratory chain in mitochondria with Mitochondrial oxidation of FADH2 eventually results in the net formation of about 1.5 ATP.
    • Likewise, oxidation of electrons from NADH yields 2.5 molecules of ATP.
    • Hence, a total of four ATP molecules are formed per cycle and ten molecules of ATP are formed through Krebs’s cycle from each molecule of acetyl CoA.

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Last modified: Friday, 22 June 2012, 5:13 AM