The document summarizes the process of beta oxidation, where fatty acids are broken down in the mitochondria to generate acetyl-CoA. There are four steps: 1) activation of fatty acids to fatty acyl-CoA in the cytosol, 2) transport into the mitochondrial matrix using carnitine shuttle, 3) beta oxidation proper involving oxidation, hydration, and thiolytic cleavage reactions to remove two-carbon acetyl-CoA units, 4) repetition of steps 3 until the fatty acid is fully broken down to acetyl-CoA, which feeds into the citric acid cycle. The process generates large amounts of ATP through production of FADH2 and NADH. Deficiencies in enzymes involved can

1. Fat Metabolism
I'm not FAT, I’ve just got a lot of Potential energy..........!!!!

2. Biochemistry 2/e - Garrett & Grisham
Copyright © 1999 by Harcourt Brace & Company
Beta Oxidation of Fatty Acids
Knoop showed that fatty acids must be degraded
by removal of 2-C units
• Albert Lehninger showed that this occurred in
the mitochondria
• F. Lynen and E. Reichart showed that the 2-C
unit released is acetyl-CoA, not free acetate
• The process begins with oxidation of the
carbon that is "beta" to the carboxyl carbon, so
the process is called"beta-oxidation"

3. Beta Oxidation
The break down of a fatty acid to acetyl-CoA
units…the ‘glycolysis’ of fatty acids.
Strictly Aerobic.
Occurs in Mitochhondria.
Acetyl Co-A is fed directly into the Kreb's
cycle.
Overproduction causes Ketosis.
Examplify Aerobic Metabolism at its most
powerful phase

4. Beta-oxidation is the process by which
fatty acids, in the form of Acyl-CoA
molecules, are broken down in mitochondria
and/or in peroxisomes to generate Acetyl-
CoA, the entry molecule for the Citric Acid
cycle.
It occurs in many tissues including liver
kidney and heart.
Fatty acids oxidation doesn't occur in the
Brain, Erythrocyets as fatty acid can't be
taken up by that organ.

5. Beta Oxidation
The beta oxidation of fatty acids
involve three stages:
1.Activation of fatty acids in the cytosol.
2.Transport of activated fatty acids into
mitochondria (carnitine shuttle).
3.Beta oxidation proper in the mitochondrial
matrix.

6. 1) Activation of FA:
This proceeds by FA thiokinase (acyl COA
synthetase) present in cytosol
Thiokinase requires ATP, COA SH, Mg++
.
The product of this reaction is FA acyl COA
and water.Three different enzymes for
short,medium & long chain FA.

7. Long chain acyl CoA traverses the inner
mitochondria membrane with a special
transport mechanism called Carnitine
shuttle.
The matrix
The cytosol

8. 1. Acyl groups from acyl COA is transferred to carnitine
to form acyl carnitine catalyzed by carnitine
acyltransferase I, in the outer mitochondrial
membrane.
2. Acylcarnitine is then shuttled across the inner
mitochondrial membrane by a translocase
enzyme.
3. The acyl group is transferred back to CoA in
matrix by carnitine acyl transferase II.
4. Finally, carnitine is returned to the cytosolic
side by translocase, in exchange for an
incoming acyl carnitine.

10. There are 4 steps in β C– oxidation
Step IStep I – Oxidation by FAD linked dehydrogenaseFAD linked dehydrogenase
Step IIStep II – Hydration by HydrataseHydratase
Step IIIStep III – Oxidation by NAD linked dehydrogenaseNAD linked dehydrogenase
Step IVStep IV – Thiolytic clevage ThiolaseThiolase

11. The first reaction is the oxidation of acyl
CoA by an acyl CoA dehyrogenase to give
α-β unsaturarted acyl CoA (enoyl CoA).
FAD is the hydrogen acceptor.

12. The second reaction is the hydration of the
double bond to β-hydroxyacyl CoA (p-
hydroxyacyl CoA).

13. The third reaction is the oxidation of β-
hydroxyacyl CoA to produce β-Ketoacyl
CoA a NAD-dependent reaction.

14. The fourth reaction is cleavage of the two
carbon fragment by splitting the bond
between α and β carbons
By thiolase enzyme.

16. The release of acetyl CoA leaves an acyl
CoA molecule shortened by 2 carbons.
 This acyl CoA molecule is the substrate
for the next round of oxidation starting
with acyl CoA dehydrogenase.
Repetition continues until all the carbons
of the original fatty acyl CoA are
converted to acetyl CoA.
In the last round a four carbon acyl CoA
(butyryl CoA) is cleaved to 2 acetyl CoA.

17. Energetics of FA oxidation
e.g. Palmitic (16C):
1.β-oxidation of palmitic acid will be
repeated 7 cycles producing 8 molecules
of acetyl COA.
2.In each cycle FADH2 and NADH+H+
is
produced and will be transported to the
respiratory chain.
FADH2 2 ATP
NADH + H+
3 ATP
So 7 cycles 5x7 = 35 ATP

18. 3. Each acetyl COA which is oxidized in
citric cycle gives 12 ATP (8 x 12 = 96
ATP)
4. 2 ATP are utilized in the activation of
fatty acid (It occurs once).
 Energy gain = Energy produced - Energy
utilized
 = 35 ATP + 96 ATP - 2 ATP = 129 ATP

19. CLNICAL ASPEST
SIDS- sudden infant death syndrome.Unexpected
death of healthy infants,usually overnight.real
cause is not known.It is now Estimated that 10%
of SIDS is due to deficiency of medium chain acyl
CoA dehydrogenase(1:10,000).
Jamaican vomiting sickness -severe convulsion
hypoglycemia,vomiting,coma and death caused
by consuption of hypoglycin A(content of unripe
ackee fruit).Inhibits the acyl CoA dehydrogenase
enzyme and thus B-oxidation.

20. Thank You