Subject: Biochemistry- ΙΙB
Topic: Beta oxidation of fatty
acids
Dr Abdul Aleem
Assistant Professor
The University of Lahore, Lahore
Beta oxidation of fatty acids
• Called so as the oxidation and splitting of two carbon units occur at
the beta-carbon atom.
Preparative steps for beta oxidation
• Co-enzyme A is a complex molecule containing B complex vitamin
pantothenic acid and a molecule of beta mercapto ethanolamaine;
this SH group forms thioester bond in acyl CoA.
Preparative step 1: Activation of
fatty acids
• Fatty acids are activated to their co-enzyme A (CoA) derivatives.
• This activation occurs in cytoplasm.
• Two high energy bonds are utilized in this reaction.
• The enzyme involved in this reaction is thiokinase or fatty acyl CoA
synthetase.
Preparative step 2: Role of
carnitine
• Fatty acids are activated in cytoplasm and beta oxidation occurs in
mitochondria.
• So, transport of fatty acids through the mitochondrial membrane is
essential.
• Long chain fatty acyl CoA can not pass through the inner
mitochondrial membrane.
• Carnitine is involved in transfer of fatty acids.
• Carnitine is beta-hydroxy-gamma-trimethyl ammonium butyrate.
• It is synthesized from lysine and methionine in liver and kidney.
Preparative step 3: Carnitine acyl
transferase
• Enzyme carnitine acyl transferase-Ι (CAT-Ι) will transfer the fatty acyl
group to the hydroxyl group of carnitine to form acyl carnitine.
• The reaction occurs on the cytosolic side of inner mitochondrial
membrane.
Preparative step 4: Translocase
• A protein translocase will carry the acyl carnitine across the
membrane to the matrix of mitochondria.
• On the matrix side, carnitine acyl transferase-ΙΙ (CAT-ΙΙ) will transfer
the acyl group back to the co-enzyme A molecule.
• Carnitine is returned to the cytosolic side by the translocase.
Beta oxidation steps
• The next 4 reactions are sequentially repeated for complete oxidation
of fatty acids.
• After one round of four complete oxidation of fatty acids, one acetyl
CoA unit is split off and acyl CoA with 2 carbon atoms less is
generated.
• This process will repeat until complete oxidation of fatty acids.
Step 1: FAD Linked dehydrogenase
• The fatty acyl CoA is dehydrogenated to a trans enoyl CoA with the
FAD accepting the hydrogen atoms.
• FADH2 when oxidized in electron transport chain will produce 1.5 ATP
molecules.
Step 2: Hydration
• This is catalyzed by an enoyl CoA hydratase to form a beta-hydroxy
fatty acyl CoA.
Step 3: NAD+ dependent
dehydrogenase
• The beta-hydroxy fatty acyl CoA is again oxidized to form beta-keto
fatty acyl CoA.
• This dehydrogenase acts only on L-isomer. The NADH when oxidized
in electron transport chain will generate 2.5 ATPs.
Step 4: Cleavage
• The beta-keto fatty acyl CoA now undergoes thiolytic cleavage,
splitting off a molecule of acetyl CoA and leaving behind a fatty acid
with 2 carbon atoms less.
Further Cycles
• The newly formed fatty acyl CoA will sequentially undergo further
cycles of steps 1, 2, 3 and 4 of beta oxidation until the fatty acid is
completely converted to acetyl CoA.
Regulation of beta oxidation
• The availability of free fatty acid regulate the net utilization through
beta oxidation
• The level of FFA, in turn, is controlled by glucagon:insulin ratio.
Glucagon increases the FFA level and insulin have opposite effect.
• CAT-1 is the regulatory of entry of fatty acid into mitochondria.
Malonyl CoA inhibits CAT-1 activity. Thus de novo synthesis of fatty
acid, the beta oxidation is inhibited.
Oxidation of odd chain fatty acids
• The odd chain fatty acids are oxidized exactly in the same manner as
even chain fatty acids.
• However, after successive removal of 2-carbon units, at the end, one
3-carbon unit, propionyl CoA is produced.
Fate of propionyl CoA
1. Carboxylase:
• Propionyl CoA is first carboxylated to D-methyl malonyl CoA.
• Biotin dependent carboxylase is used
• One ATP molecule is utilized to supply energy.
2. Racemase:
• Racemase converts D-methyl malonyl CoA to give L-methyl malonyl
CoA.
Conti…..
3. Mutase:
• L-methyl malonyl CoA is arranged to form succinyl CoA by L-methyl
malonyl CoA mutase.
• The reaction needs malonyl CoA mutase.
4. The succinyl CoA then enters TCA cycle, finally converted to
oxaloacetate, and is used for gluconeogenesis.
5. Propionyl CoA is also derived from the metabolism of valine and
isoleucine.
Energetics of beta oxidation
Summary of beta oxidation
Reference book
• Text book of Biochemistry by DM Vasudevan. Sixth edition.
• Ch# 11
• Page# 131-134.
