This document provides a comprehensive overview of lipid metabolism, detailing the processes of β-oxidation of fatty acids, ketone body formation, and de novo fatty acid synthesis. It explains the biochemical significance of lipids, the types of lipids, and the various disorders related to lipid metabolism. The document also outlines the metabolic pathways involved in fat catabolism, emphasizing the energetics of fatty acid oxidation, particularly using palmitic acid as an example.

1. LIPID METABOLISM
- Prepared by
Ms. Christina Viju
Assistant Professor
UNIT 3

2. Contents
Lipid metabolism
• β-Oxidation of saturated fatty acid (Palmitic acid)
• Formation and utilization of ketone bodies;
ketoacidosis
• De novo synthesis of fatty acids (Palmitic acid)
• Biological significance of cholesterol and conversion of
cholesterol into bile acids, steroid hormone and
vitamin D
• Disorders of lipid metabolism: Hypercholesterolemia,
atherosclerosis, fatty liver and obesity

3. What is a Lipid?
❑ These are nonpolar organic compounds which
❑ They are generally insoluble to water, but soluble to nonpolar solvent
like; - Chloroform - Acetone – ether - benzene
❑ It contains a carbonyl group (-COOH)
What are the functions of lipids?
❑ As membrane structural component.
❑ As intracellular storage depot of metabolic fuel. As
transport form of metabolic fuel.
❑ As protective form of the cells of many bacteria,
leaves of higher plants, exoskeleton of insects and
the skin of vertebrates.
❑ A regulatory substances.
❑ As transport form of some neurotransmitters.
❑ As receptors in nerve ending membranes.
❑ As determinants of immunological specificity.
❑ Enzyme co-factors

4. Types of Lipids
The four main groups of lipids include:
1. Fatty acids (saturated and unsaturated)
2. Glycerides (glycerol-containing lipids)
3. Nonglyceride lipids (sphingolipids, steroids, waxes)
4. Complex lipids (lipoproteins, glycolipids)
Triglyceride degradation
Triglycerides are degraded by lipases to form free fatty acids and glycerol

7. Lipid Catabolism
Catabolism – refers to several reactions that
produce energy
- it is a breakdown of complex organic compounds into a
simpler compounds.
• It is related to carbohydrate metabolism because the
carbohydrates will turn into fatty acids and glycerol.
• The glycerol will participate is glycolysis.
• It is an important process because the produced Fatty acids
will participate in fatty acid oxidation.
• Fats are important source of energy as (1gm of fat gives 9 kcal
energy).
• Mainly as triacylglycerols (triglycerides) in adipose cells
• Constitute 84% of stored energy: Protein - 15%; Carbohydrate
(glucose or glycogen) - <1%

9. Beta Oxidation of Fatty Acid
The break down of a fatty acid to acetyl-CoA (Acetyl Coenzyme A)
The end product of each cycle is the fatty acid shortened by 2 carbons
and acetyl CoA.
The series of reactions is also known as the betaoxidation pathway
because the major reaction site is the beta-carbon
➢ Happens in the mitochondrial membrane
➢ The fatty acids must be activated and turned into acetyl- CoA
➢ Process is strictly aerobic
➢ After production Acetyl-CoA is fed directly into the Krebs cycle

10. ➢ It occurs in many tissues including liver, kidney and
heart.
➢ Fatty acids oxidation doesn't occur in the
brain
There are several types of fatty acids oxidation.
(1) β- oxidation of fatty acid
(2) α- oxidation of fatty acids
(3) ω- oxidation of fatty acids
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

11. 1) Activation of FA:
This proceeds by FA thiokinase (acyl COAsynthetase) present in cytosol
Thiokinase requires ATP
, CoA-SH, Mg++.
The product of this reaction is FA acyl COA and Water

13. 2- Transport of fatty acyl CoA from cytosol into mitochondria:
•Long chain acyl CoA traverses the inner mitochondria membrane
with a special transport mechanism called Carnitine shuttle.

14. (rate-limiting step)
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

15. R =
PALMITIC ACID (C-16)

16. 3. Proper of β – oxidation in the mitochondrial
matrix
There are 4 steps in β – oxidation
Step I – Oxidation by FAD linked dehydrogenase
Step II – Hydration by Hydratase
Step III – Oxidation by NAD linked dehydrogenase
Step IV – Thiolytic clevage Thiolase

17. Step I: 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

18. Step II: The second reaction is the hydration of the double
bond to β- hydroxyacyl CoA

19. Step III: The third reaction is the oxidation of β-hydroxyacyl CoA to
produce β-Ketoacyl CoA a NAD-dependent reaction

20. Step IV: Thiolytic Cleavage
The fourth reaction is cleavage of the two carbon fragment by splitting
the bond between α and β carbons by thiolase enzyme

21. ➢ 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 get 2 acetyl CoA

22. Energetics of FA oxidation
E.g. Palmitic Acid (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+ is produced and will be
transported to the respiratory chain.
• FADH2= 1.5 ATP
• NADH + = 2.5 ATP
Total= 4 ATP
So 7 cycles, 4 x 7 cycles = 28 ATP
3. Each acetyl CoA which is oxidized in citric cycle gives 12 ATP
So, 8 molecules x 12 = 96 ATP
4. 2 ATP are utilized in the activation of fatty acid (It occurs once).
❑Energy gain = Energy produced – Energy utilized
= 28 ATP + 96 ATP - 2 ATP = 122 ATP