β Oxidation and Biosynthesis - Fatty Acid Metabolism
fatty acid metabolism, beta oxidation, biosynthesis

Fatty Acid Metabolism

β Oxidation Enzyme Biosynthesis Enzyme
Location Mitochondria Cytosol
Fatty acyl-X ↔ Enoyl-X AD = Acyl-CoA dehydrogenase ER = Enoyl-ACP reductase
Enoyl-X ↔ Hydroxylacyl-X EH = Enoyl-CoA hydratase DH = Hydroxylacyl-ACP Dehydratase
Hydroxylacyl-X ↔ Ketoacyl-X HAD = Hydroxylacyl-CoA dehydrogenase KR = Ketoacyl-ACP reductase
Ketoacyl-X ↔ Fatty(n-2) acyl-X KT = Ketoacyl-CoA thiolase KS = Ketoacyl-ACP synthase
note: X = -CoA for β oxidation, -ACP for biosynthesis.
  • 10% of sudden infant death syndrome (SIDS) infants are deficient in medium-chain AD (MCAD).

Other Enzymes

  • β Oxidation fatty acid activation:
    • AS = Acyl-CoA synthase = Thiokinase
    • Converts fatty acid → fatty acyl-CoA
  • Biosynthesis fatty acid activation:
    • MAT = Malonyl/Acetyl-CoA-ACP transacylase.
    • Converts acetyl-CoA (or malonyl-CoA) → acetyl-ACP (or malonyl-ACP)
  • TE = Thioesterase

Transport

  • Carnitine transport system: Fatty acyl-CoA from cytosol → mitocondria.
    1. Cytosol acyl-CoA → cytosol acyl-carnitine
    2. Cytosol acyl-carnitine → mitochondrial acyl-carnitine (using the carnitine carrier protein)
    3. Mitocondrial acyl-carnitine → mitochondrial acyl-CoA
    4. Mitochondrial carnitine → cytosol carnitine (using the carnitine carrier protein)
  • Tricarboxylate transport system: Acetyl CoA out of mitochondria.
    1. Mitochondrial acetyl-CoA + oxaloacetate → mitochondrial citrate
    2. Mitochondrial citrate → cytosol citrate (via tricarboxylate transport system)
    3. Cytosol citrate → acetyl-CoA + oxaloacetate (ATP-citrate lyase)
    4. Cytosol oxaloacetate → malate → pyruvate (1. malate DH, 2. malic enzyme)
    5. Cytosol pyruvate → mitochondrial pyruvate
    6. Mitochondrial pyruvate → oxaloacetate (pyruvate carboxylase)

Fatty acid synthesis

  • Occurs in the cytosol (in contrast to β-oxidation which occurs in the mitochondria).
  • Mechanism is almost the exact opposite of β-oxidation:
    1. Start with acetyl-CoA.
    2. Change acetyl-CoA → acetyl-ACP.
    3. Make acetoacetyl-ACP by adding malonyl-ACP (decarboxylates into the enolate ion of acetyl-ACP).
    4. Get rid of β-keto group by reduction to -OH (reductase), eliminate water (dehydrase), then reduction of double bond (reductase).
    5. Repeat by adding another malonyl-ACP.

Triglyceride synthesis

  • Triglyceride = triacylglycerol = neutral fats.
  • Glycerol + 3Fatty acids = triacylglycerol.
  • Adipocytes are specialized to make and store triglycerides.