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Once inside the mitochondria, the ?-oxidation of fatty acids occurs via four recurring steps:
- Oxidation by FAD
- Hydration
- Oxidation by NAD+
- Thiolysis
Beta oxidation is the process by which fatty acids, in the form of Acyl-CoA molecules, are broken down in mitochondria and/or in peroxisomes to generate Acetyl-CoA, the entry molecule for the Krebs cycle.(Figure)
Four recurring steps
Once inside the mitochondria, the ?-oxidation of fatty acids occurs via four recurring steps:
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Description
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Diagram
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Enzyme
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End product
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Dehydrogenation by FAD: The first step is the oxidation of the fatty acid by Acyl-CoA-Dehydrogenase. The enzyme catalyzes the formation of a double bond between the C-2 and C-3.
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acyl CoA dehydrogenase
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trans-?2-enoyl-CoA
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Hydration: The next step is the hydration of the bond between C-2 and C-3. The reaction is stereospecific, forming only the L isomer.
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enoyl CoA hydratase
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L-?-hydroxyacyl CoA
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Oxidation by NAD+: The third step is the oxidation of L-?-hydroxyacyl CoA by NAD+. This converts the hydroxyl group into a keto group.
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L-?-hydroxyacyl CoA dehydrogenase
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?-ketoacyl CoA
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Thiolysis: The final step is the cleavage of ?-ketoacyl CoA by the thiol group of another molecule of CoA. The thiol is inserted between C-2 and C-3.
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?-ketothiolase
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An acetyl CoA molecule, and an acyl CoA molecule, which is two carbons shorter
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This process continues until the entire chain is cleaved into acetyl CoA units. The final cycle produces two separate acetyl CoA's, instead of one acyl CoA and one acetyl CoA. For every cycle, the Acyl CoA unit is shortened by two carbon atoms. Concomitantly, one molecule of FADH2, NADH and acetyl CoA are formed.
Energy yield
The ATP yield for every oxidation cycle is 14 ATP (according to the P/O ratio), broken down as follows:
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Source
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ATP
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Total
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1 FADH2
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x 2 ATP
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= 2 ATP (some sources say 1.5 ATP)
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1 NADH
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x 3ATP
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= 3 ATP (some sources say 2.5 ATP)
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1 acetyl CoA
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x 12 ATP
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= 12 ATP (some sources say 10 ATP)
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TOTAL
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= 17 ATP
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For an even-numbered saturated fat (C2n), n - 1 oxidations are necessary and the final process yields an additional acetyl CoA. In addition, two equivalents of ATP are lost during the activation of the fatty acid. Therefore, the total ATP yield can be stated as:
(n - 1) * 14 + 10 - 2 = total ATP
For instance, the ATP yield of palmitate (C16, n = 8) is:
(8 - 1) * 14 + 10 - 2 = 106 ATP
Represented in table form:
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Source
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ATP
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Total
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7 FADH2
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x 2 ATP
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= 14 ATP
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7 NADH
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x 3 ATP
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= 21 ATP
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8 acetyl CoA
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x 12 ATP
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= 96 ATP
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Activation
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= -2 ATP
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NET
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= 129 ATP
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For sources that use the larger ATP production numbers described above, the total would be 129 ATP equivalents per palmitate.
Beta-oxidation of unsaturated fatty acids changes the ATP yield due to the requirement of two possible additional enzymes
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