This document summarizes fatty acid oxidation through beta-oxidation. It discusses how fatty acids are broken down into acetyl-CoA in the mitochondria, generating energy in the form of ATP. Key points covered include the carnitine shuttle transport system, reactions of beta-oxidation, and oxidation of odd-chain and unsaturated fatty acids. Deficiencies in carnitine or the carnitine shuttle enzymes can impair fatty acid breakdown.

1. Β-OXIDATION OF FATTY ACIDS
MARIA GUL
LECTURER
JIPS, LAHORE

2. INTRODUCTION
 The yield from the complete oxidation of fatty acids to CO2
and H2O is 9 kcal/g fat (as compared to 4 kcal/g protein or
carbo - hydrate.
 Fatty acids are also supplied to tissues by lipoproteins
 Hormone-sensitive lipase removes a fatty acid from carbon
1 and/or carbon 3 of the TAG.
 Additional lipases specific for diacylglycerol or
monoacylglycerol remove the remaining fatty acid(s).
 When TAGs degradation is ON , Fatty acid synthesis is
turned OFF.

3.  Glycerol released from TAGs is transported to liver,
converted to DHAP and participate
glycolysis/gluconeogenesis
 Fatty Acid move by binding to plasma Albumin, Transported
to tissues . In tissue they are activated by binding to their
CoA derivatives and oxidized for energy

4. B-OXIDATION OF FATTY ACIDS
 The major pathway for catabolism of fatty acids is a
mitochondrial pathway called β-oxidation
 In this two-carbon fragments are successively removed from the
carboxyl end of the fatty acyl CoA, producing acetyl CoA,
NADH, and FADH2.
 Fatty acyl coA with more then 12 carbons (Activated form) is
transported into the mitochondrial matrix through Carnitine
shuttle as CoA cannot cross the inner Mitochondrial membrane
 Fatty acyl CoA synthetase (Thiokinase) converts a F.A to its
active form by adding CoA using 2 ATP molecules
 (Brain have Mitochondria but cannot use FA as energy source).

6. CARNITINE SHUTTLE
 CPT-1 (carnitine palmitoyl transferase I) transfer the acyl
group from Fatty acyl coA to carnitine & form Acyl
Carnitine
 Carnitine/Acyl carnitine Translocase facilitates transport
 CPT-II Transfer acyl group from carnitine to CoA
 Malonyl CoA inhibits CPT-I, prevent the entry of acyl
groups into the Mitochondrial matrix
 Carnitine is obtained primarily from meat products
 It is also synthesized in liver and kidney from Lysine and
methionine amino acids
 Skeletal muscles contain 97% of all carnitine in the body

7. CARNITINE DEFICIENCY
 Decreased ability to use F.A as metabolic fuel
 It may occur secondarily, due to
 1. Liver diseases (Decreased synthesis of carnitine)
 2. Malnutrition/ vegetarian diet
 3. Pregnancy, infection, burns, trauma
 4.Hemodialysis as it removes carnitine from blood
 CPT-I deficiency affects liver (impairs
gluconeogenesis) and leads to Hypoglycemia, coma
or death

8.  CPT-II deficiency occurs primarily in cardiac and
skeletal muscles
 It causes Cardiomyopathy, muscle weakness with
myoglobinemia
 Treatment includes supplements of Medium chain
fatty acids and carnitine/ enzyme replacement
therapy
 Fatty acids shorter than 12 carbons can cross the
inner mitochondrial membrane without the aid of
carnitine or the CPT system. Once inside the
mitochondria, they are activated to their CoA
derivatives by matrix enzymes, and are oxidized

9. REACTIONS
 It consists of 4 reactions involving β carbon
 1. Oxidation: Produce FADH2
 2. Hydration
 3. 2nd oxidation: Produces NADH
 4. Thiolytic cleavage: release one acetyl coA
 Net: FADH2 = 1
 NADH = 1
 Acetly coA = 1 (it yields 12 ATPs by TCA cycle)

12. NET ENERGY YIELD FROM PALMITATE
 Oxidation of molecule of palmitoyl CoA to CO2 and
H2O produces 8 acetyl CoA, 7 NADH, and 7
FADH2, from which 131 ATP can be generated;
 however, activation of the fatty acid requires 2 ATP.
Thus, the net yield from palmitate is 129 ATP
 Activation of palmitate to palmitoyl CoA requires the
equivalent of 2 ATP.

13. OXIDATION OF ODD CHAIN
FATTY ACIDS
 Initial steps are same like even
number chains
 Final step produces 3 carbon
compound Propionyl coA which
enters TCA cycle in the form of
Succinyl CoA
 This is the only example of a
glucogenic precursor generated
from fatty acid oxidation.

14. OXIDATION OF UNSATURATED FATTY ACIDS
 Yields less energy as Unsaturated F.A are less
highly reduced.(produces few reducing equivalents)
 Oxidation of monounsaturated fatty acids, such as
18:1(9) (oleic acid) requires one additional enzyme,
3,2-enoyl CoA isomerase, which converts the 3-
trans derivative obtained after three rounds of β-
oxidation to the 2-trans derivative required as a
substrate by the enoyl CoA hydratase. Oxidation o
polyunsaturated fatty acids, such as 18:2(9,12)
(linoleic acid), requires an NADPH-dependent 2,4-
dienoyl CoA reductase in addition to the isomerase.

16. Β-OXIDATION IN PEROXISOMES
 Very-long-chain fatty acids (VLCFA), or those 22 carbons
long or longer, undergo a preliminary β-oxidation in
peroxisomes. The shortened fatty acid (linked to
carnitine) diffuses to a mitochondrion for further
oxidation.
 In contrast to mitochondrial β-oxidation, the initial
dehydrogenation in peroxisomes is catalyzed by an
FAD-containing acyl CoA oxidase. The FADH2 produced
is oxidized by molecular oxygen, which is reduced to
H2O2; thus, no ATP is generated by this step. The H2O2
is reduced to H2O by catalase.
 Genetic defects in the ability to target matrix proteins to
peroxisomes (resulting in Zellweger syndrome —lead to
accumulation of VLCFA in the blood and tissues

17. OXIDATION OF VLCFA

18. ΑLPHA-OXIDATION
 Branched chain, 20 carbon fatty acid (phytanic
acid) undergo α-oxidation
 Its beta carbon is not free as it contains Methyl
group
 Carbon 1 is hydroxylated by Phatonyl coA α-
hydroxylase (phyH)
 So carbon 1 is released as CO2
 19 carbon pristanic acid is activated to its coA
derivative and undergo β-oxidation