mehta4748 - Fatty Acid Oxidation and Ketone Bodies Medical...

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Fatty Acid Oxidation and Ketone Bodies Medical Biochemistry Lectures #47 and #48
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    OXIDATION OF FATTY ACIDS:   KETOGENESIS • The initial event in the utilization of fat as  an  energy  source  is  the  hydrolysis  of  triacylglycerol by lipases
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• Epinephrine, norepinephrine, glucagon, and  adrenocorticotropic  hormone  stimulate  the  adenylate cyclase of adipose cells, and thus  cause lipolysis.
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Fatty acids are synthesized and  degraded by different mechanisms: • Fatty acids are both oxidized to acetyl-CoA  and synthesized from acetyl-CoA.   Although the staring material of one  process is identical to the product of the  other, fatty acid oxidation is not the simple  reverse of fatty acid biosynthesis.  It is an  entirely different process taking place in  separate compartment of the cell.  This  allows each process to be individually  controlled.
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Fatty acids are synthesized and  degraded by different mechanisms:         Synthesis Oxidation Cytosol Intermediates are covalently linked to ACP Fatty acid synthase contain multienzyme activities Utilizes NADP+ as coenzyme Requires both ATP and bicarbonate ion Mitochondrial matrix Bonded to CoA Degradative enzymes are not associated Utilizes NAD+ and FAD as coenzymes Generates ATP Aerobic process
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Step 1:  Activation of fatty acids to acyl-CoA:   Acyl-CoA  synthetases are found in the endoplasmic reticulum,  peroxisomes, and inside and on the outer membrane of  mitochondria.  Several acyl-CoA synthetases have been  described, each for fatty acids of different chain length. R-COO - + CoA + ATP + H 2 0 Acyl CoA + AMP + 2P i + 2H +
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Step 2:  Long-chain fatty acids penetrate inner  mitochondrial membrane as carnitine derivatives.    Carnitine (ß-hydroxy-g-trimethylammonium  butyrate) is widely distributed and abundant in  muscle.  Carnitine palmitoyltransferase-I, present in  the outer mitochondrial membrane, catalyzes the  following reaction:  
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Step 3:  ß-oxidation of fatty acids involves successive cleavage with  release of acetyl-CoA.   Fatty acid oxidase are found in the  mitochondrial matrix or inner membrane adjacent to the respiratory  chain in the inner membrane.
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Oxidation of unsaturated fatty acids occurs by a modified β -oxidation pathway:
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  Oxidation of fatty acids produces a large quantity of ATP:
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mehta4748 - Fatty Acid Oxidation and Ketone Bodies Medical...

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