In detail description about beta oxidation of fatty acid with regulation and clinical importance. easy to study and write in exams for students.

1. BETA OXIDATION OF FATTY
ACIDS
Dr SANA PARVEEN MBBS,MD

2. • β oxidation is major pathway of oxidation of
fatty acids.
• DEF: The oxidation of the hydrocarbon chain
of Fatty acid by a sequential cleavage of two
carbon atoms.
• It is called βoxidation, because the oxidation
and splitting of two carbon units occur at the
beta-carbon atom.

4. Preparative Steps for Beta Oxidation
• Before oxidation fatty acids require to be -
1.Activated
2.Transported into mitochondria

6. Fatty Acids Activation
• Fatty acids are activated to their co-enzyme A
(CoA) derivative.
• This activation is taking place in cytoplasm
• Enzyme : thiokinase or fatty acyl CoA synthetase
• ATP is hydrolyzed to AMP and Ppi using energy
of two high energy bonds .
• Two inorganic phosphates are used
• Three different enzymes, one each for short
chain, medium chain and long chain fatty acids
have been identified.

7. Transport of Activated Fatty acid
• For transport two molecules are required
1.Carnitine
2.Translocase

8. Carnitine:
• Carnitine is beta-hydroxy gamma trimethyl
ammonium butyrate,
(CH3)3–N+–CH2–CHOH–CH2–COOH.
• It is synthesized from lysine and methionine in
liver and kidney.

9. Role of Carnitine
• Fatty acids are activated in the cytoplasm; but
the beta oxidation is in mitochondria.
• Carnitine a transporter, is involved in transfer
of long chain of fatty acids.
• Medium chain and short chain fatty acids do
not require carnitine for transport across the
inner mitochondrial membrane.
• So medium chain and short chain fatty acids
are easily oxidized.

11. Carnitine Acyl Transferase
• The enzyme carnitine acyl transferase-I (CAT-
I/CPT -I) 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.

12. Translocase
• A protein translocase will carry the acyl
carnitine across the membrane to the matrix
of mitochondria.
• On the matrix side of the membrane another
enzyme, carnitine acyl transferase-II (CAT-II)
will transfer the acyl group back to co-enzyme
A molecule
• Carnitine is returned to the cytosolic side by
the translocase.

14. Beta Oxidation
• After the penetration of the acyl-CoA into
mitochondria, it undergoes β-oxidation.
• A saturated acyl-CoA is degraded by a
repeated sequence of four reactions
• 1. Oxidation by FAD
• 2. Hydration
• 3. Oxidation by NAD
• 4. Cleavage.

16. Step 1:Oxidation by FAD
• The first reaction is the oxidation of acyl-CoA
by an acyl-CoA dehydrogenase to give an Δ2-
trans enoyl-CoA
• The coenzyme for the dehydrogenase is FAD
which is converted to FADH2.
• FADH2 when oxidised in electron transport
chain will produce 1.5 ATP molecules.

17. Step 2:Hydration
• The next step is the hydration (addition of
water) of the double bond between C2 and C3
by Δ2-enoyl-CoA hydratase to form β-hydroxy
acyl-CoA.

18. Step 3:Oxidation by NAD
• The β-hydroxy derivative undergoes second
oxidation reaction catalyzed by β-
hydroxyacyl-CoA dehydrogenase to form β-
ketoacyl-CoA and generates NADH.
• The NADH when oxidised in electron transport
chain will generate 2.5 ATPs.

19. Step 4:Cleavage
• Finally β-ketoacyl-CoA is split at the β-carbon
by thiolase to yield acetyl-CoA and an acyl-
CoA which is shorter by two carbon atoms.

20. • The new acyl-CoA, containing two carbons less
than the original, re-enters the β-oxidation
pathway at reaction catalyzed by acyl-CoA
dehydrogenase .
• The process continues till the fatty acid
degraded completely to acetyl-CoA.

21. Energetics of Beta Oxidation
(ATPYield)
• Palmitic acid (16 C) needs 7 cycles of beta oxidation .
• it gives rise to 8 molecules of acetyl CoA.
• Every molecule of acetyl CoA when oxidised in the TCA cycle
gives 10 molecules of ATP . Each molecule of
• The energy yield from one molecule of palmitate calculated
as:
• 8 acetyl CoA × 10 = 80 ATP
• 7 FADH2 × 1.5 = 10.5 ATP
• 7 NADH × 2.5 = 17.5 ATP
• Gross total = 108 ATP
• Net yield = 108–2 = 106 ATP
• In the initial activation reaction, the equivalents of 2 high
energy bonds are utilised.
FADH2=1.5ATP
NADH2=2.5ATP

24. Regulation of Beta Oxidation
• The availability of free fatty acid (FFA)
regulates the net utilisation through beta
oxidation.
• The level of FFA is controlled by
glucagon:insulin ratio.
• Glucagon increases FFA level and insulin has
the opposite effect.

25. Regulation of Beta Oxidation
• CAT-I is the regulator of entry of fatty acid into
mitochondria.
• Malonyl-CoA is an inhibitor of CAT-I.(intermediate
of fatty acid synthesis)
• In well fed conditions concentration of malonyl-
CoA increases which inhibits CAT-I and leads to
decrease in fatty acid oxidation.
• In starvation, reverse occurs i.e. decreased
malonyl-CoA will remove CAT I inhibition allowing
more AcylCoA to be oxidized.

26. Clinical Applications
• Carnitine deficiency:
 seen in preterm infants & hemodialysis patients
Dietary deficiency of essential amino acids (lys,met)
impaired fatty acid oxidation is noticed.
more glucose is utilized, resulting in episodes of
hypoglycemia.
• Deficiency of translocase:
 It leads to defective metabolism of long chain fatty
acids.
In this condition, muscle cramps are precipitated by
fasting, exercise and high fat diet.

27. • CPT-I deficiency :affects only the liver,
resulting in reduced fatty acid oxidation and
ketogenesis, with hypoglycemia.
• CPT-II deficiency :affects primarily skeletal
muscle and, when severe, the liver.
• Oral hypoglycemic drugs(glibenclamide and
tolbutamide), used in the treatment of type 2
diabetes mellitus may also inhibit transferases
enzyme( CPT-I).
• Treatment is to avoid LCFA and substitute with
SCFA &MCFA .

28. Jamaican vomiting syndrome
• Jamaican vomiting syndrome is due to a toxin
called hypoglycin ,present in unripe ackee fruit
• Hypoglycin inhibits fatty acyl co A
dehydrogenase and impairs β oxidation
• Hypoglycemia,vomiting ,convulsions & coma
are seen.

29. Medium chain acyl
CoA dehydrogenase deficiency
• Of all enzymes of beta oxidation MCAD deficiency is most
common
• usually manifests early in life by 2 years
• Patients have vomiting, lethargy, fasting hypoglycemia
etc.many ultimately go into coma
• Hypoglycemia is not ketotic
• There is compensatory increase in ω oxidation which
produces small to medium chain dicarboxylic acids that are
excreted in urine as glycine & carnitine conjugates
• Treatment is high carbohydrate diet & carnitine
supplementation to compensate urinary loss.
• Most cases of SIDS are found to be due to MCAD deficiency.

30. References:
• Textbook of Biochemistry for medical students-DM Vasudevan
• Textbook of Medical biochemistry –Dr S.K.Gupta