Biochemistry

Fatty Acid Degradation

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BETA OXIDATION

  • Occurs in liver and peripheral tissues (mitochondrial matrix)
  • Occurs under low energy conditions (starvation, insulin:glucagon ratio is low)
  • NOT reverse of fatty acid synthesis

TRIACYLGLYCEROL (TAG)

  • Stored in adipose and liver (circulates as lipoprotein)
  • TAG breaks down to glycerol and fatty acids
  • Fatty acids exit adipose and travel to muscle for degradation (provide ATP when energy is low)

TYPES OF FATTY ACIDS

  • Degradation pathways differ depending on chain length and saturation

Saturated long chain fatty acids

  • Model pathway in diagram

Unsaturated fatty acids

  • Already partially oxidized: yield less FADH2 and ATP
  • Req. different enzymes to work with additional double bonds

Branched chain fatty acids

  • Alpha-oxidation: produce acetyl CoA and propionyl CoA

Medium and short chain fatty acids

  • Can be 6-12C long
  • Do NOT need carnitine shuttle to enter matrix
  • Req. medium-chain acyl CoA dehydrogenase (MCAD) for oxidation step

FATTY ACIDS DELIVERY (ADIPOSE TO MUSCLE)

  1. Fatty acids travel from adipose to muscle cell
  2. Fatty acid transporter transports fatty acids into cytosol
  • Carnitine transporter moves carnitine into cytosol
  1. Fatty acyl CoA synthetase: Fatty acid + CoA + ATP –> Fatty acyl CoA + AMP

Carnitine

  • Specialized carrier that transports fatty acids within cell
  • “Car” in carnitine ~ shuttle

CARNITINE SHUTTLE

  1. Carnetine acyl-transferase I (CAT-1): Fatty acyl CoA + Carnitine –> Fatty acyl-carnitine + CoA
  2. Fatty acyl-carnitine enters matrix
  3. CAT-2 (embedded in inner membrane): Fatty acyl-carnitine –> Carnitine + Fatty acyl CoA

BETA-OXIDATION

  • Breaks down fatty acids in 2C increments (acetyl CoA) + shorter chain fatty acid
  • Req. four reactions per 2C increment
  • All reactions occur at beta-carbon (beta-oxidation)

Each 2C increment

i. Oxidation

  • Acyl CoA dehydrogenases (ACAD): family of chain-length specific enzymes
  • Releases FADH2 (~ 2 ATP via oxidative phosphorylation)
    ii. Hydration
    iii. Another oxidation
  • Releases NADH (~ 3 ATP via oxidative phosphorylation)
    iv. Release of 2C (acetyl CoA)
  • Acetyl CoA can enter fatty acid synthesis or citric acid cycle
  • Citric acid cycle: 1 ATP, 1 FADH2 & 3NADH (HIGH ENERGY YIELD!)

ODD CHAIN FATTY ACIDS

  • Final products: 2C Acetyl CoA + 3C propionyl CoA

Propionyl CoA Breakdown

  • Propionyl CoA carboxylase (ABC-carboxylase reaction):
    Propionyl CoA + ATP + biotin + CO2 –> Methylmalonyl CoA (4C)
  • Methyl-malonyl CoA mutase (req. Vit B12 cobalamin): Methylmalonyl CoA –> Succinyl CoA

Product: Succinyl CoA (4C)

  • Citric acid cycle intermediate
  • Gluconeogenic intermediate: only fatty acid that can be converted to glucose

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