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Fatty Acid Catabolism

Beta-Oxidation & Ketogenesis

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Energy Storage

Fat is a major energy source in the body

  • major fuel for exercise

  • FAs yield more kcal (ATP) per gram than CHO or protein oxidation

  • the more H atoms contained in a fuel nutrient, the more ATP produced per molecule oxidized

    • 1 molecule of glucose --> 36 ATP​

    • 1 molecule palmitate --> 129 ATP

Storage in a typical 70kg man...

  • 100,000 kcal in TAGs

  • 25,000 kcal in protein

  • 600 kcal in glycogen

  • 40 kcal in glucose

Fatty Oxidation in Mitochondria

Stage 1: activate fatty acid

  • attach CoASH to the COOH of fatty acid

  • uses 2 ATP equivalents

  • because fat is stored in cytoplasm, released FA must be activated and transferred to mitochondria to be oxidized 

next two stages are important dehydration steps

  • occurs in the mitochondrial matrix

  • series of reactions known as beta-oxidation

    • because the beta carbon (C3 from the carboxyl end) is the most highly oxidized)​

    • the carbon chain is cut between the alpha and beta carbons

    • this series is repeated

    • goal is to break off 2C units as acetyl CoA

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First, activated long chain FAs have to be transported into the mitochondrial matrix

  • carnitine helps transport through inner mitochondrial membrane

 

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CARNITINE/ACYL TRANSFERASE SHUTTLE SHUTTLE

  • transfers an acyl-CoA from the cytosol into the inner mito membrane

    • acyl-CoA cannot cross by itself​

    • acyl group is transferred to carnitine

    • acyl-carnitine is transported across mito membrane into the inner mito membrane by carnitine translocase

    • inside the matrix, the acyl-carnitine becomes acyl-CoA and carnitine again

    • short and medium chain FAs do not need carnitine, they are tiny enough to pass through

 

β-Oxidation

  • 1 ATP used to activate, but 2 ATP equivalents

  • the FA is hydrolyzed two carbons at a time

    • product is acetyl CoA and the fatty acid (minus 2 carbons)​

    • the remaining fatty acid is still activated because of the addition of CoASH in the final step

  • This is repeated until hydrolysis is completed

    • 7 turns needed​

  • 1 FADH2 and 1 NADH + H with each 2 carbons removed

    • acetyl CoA goes to the TCA

    • FADH2 and NADH + H go to ETS

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Example: β- oxidation of palmitate (C16)

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What happens when there is an odd number of carbons in a FA chain? 

  • the final step of the degradation of fatty acids with an odd number of carbons produces:

    • acetyl-CoA​

    • propionyl-CoA

      • can be converted into succinyl-CoA and enter the TCA cycle​

Ketogenesis

  • Overflow pathway for acetyl CoA

  • acetyl CoA accumulates more than TCA cycle can process

  • high rate of FA oxidation in the liver

  • proportional to the rate of FA oxidation

  • in mitochondria

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  • Ketone bodies: 

    • acetone​

    • acetoacetate

    • beta-hydroxybutyrate

  • concentration of ketone bodies increase during

    • starvation​

    • uncontrolled diabetes

    • low CHO intake

  • liver makes ketone bodies but cannot utilize them

    • brain and muscle​

  • releases them to blood

    • dissolves well in blood​

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©2023 by Syracuse University Dr.Margaret Voss

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