All concepts about metabolism of lipids

1. Metabolism
of lipids

2. Introduction
• Reserves of stored triglycerides are mobilized as needed for
energy production.
• The triglycerides are hydrolyzed to fatty acids and glycerol and
enter the blood stream.
• Glycerol is converted to glycerol- 3 phosphate and then to
dihydroxyacetone phospahte, which enters glycolysis for
energy production.
• Free fatty acids are converted to fatty acyl CoA molecules,
which are broken down to acetyl CoA by beta oxidation. The
acetyl CoA may be used for energy production by way of the
citric acid cycle and the electron transport chain.

3. Synthesis of Triacylglycerol

4. • Triacylglycerol (TG) synthesis mostly occurs in Iiver
and adipose tissue, and to a lesser extent in other
tissues.
• Fatty acids and glycerol must be activated prior to the
synthesis of triacylglycerols.

7. Synthesis of glycerol 3.phosphate
• Two mechanisms are involved for the synthesis of
glycerol 3-phosphate
1 . In the liver, glycerol is activated by glycerol kinase.
This enzyme is absent in adipose tissue.
2. In both liver and adipose tissue, glucose serves as a
precursor for glycerol 3-phosphate.

8. • Dihydroxyacetone phosphate (DHAP) produced in
glycolysis is reduced by glycerol 3-phosphate
dehydrogenase to glycerol 3-phosphate.
• Addition of acyl groups to form TG, glycerol 3-
phosphate acyltransferases catalyzes the transfer of
an acyl group to produce lysophosphatidic acid.

9. • DHAP can also accept acyl group, ultimately resulting
in the formation of lysophosphatidic acid.
• Another acyl group is added to lysophosphatidic acid
to form phosphatidic acid ( 1,2-diacylglycerol
phosphate).
• The enzyme phosphatase cleaves off phosphate of
phosphatidic acid to produce diacylglycerol.
• lncorporation of another acyl group finally results in
synthesis of triacylglycerol.

10. • The three fatty acids found in triacylglycerol are not of
the same type.
• A saturated fatty acid is usually present on carbon 1
• an unsaturated fatty acid is found on carbon 2, and
carbon 3 may have either

11. Lipolysis:

13. Oxidation of Fatty Acids
 Fatty acids are an important source of
energy
 Oxidation is the process where energy
is
produced by degradation of fatty acids
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

14. Def:
 Beta-Oxidation may be defined as the oxidation of fatty acids
on the β-carbon atom.
 This results in the sequential removal of a two
carbon fragment, acetyl CoA.

15. β - oxidation of fatty acid
 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 – enters TCA cycle
 It occurs in many tissues including liver kidney and heart.

16. Stages
 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

17. 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.

18. 2- Transport of fatty acyl CoA from cytosol into
mitochondria ( rate limiting step)
• Long chain acyl COA traverses in mitochondria membrane with
a special transport mechanism called Carnitine shuttle
Matrix

20. 2-Transport of acyl CoA into the mitochondria (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.

21. 3. Proper of β – oxidation in the
mitochondrial matrix
• Step I – Oxidation by FAD linked dehydrogenase
• Step II – Hydration by Hydratase
• Step III – Oxidation by NAD linked dehydrogenase
• Step IV – Thiolytic clevage Thiolase

22. • 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.

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

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

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

27. • 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.

28. Alpha oxidation
 Oxidation of fatty acids on α-carbon atom is known as α-
oxidation.
 In this, removal of one carbon unit from the carboxyl end.
 Energy is not produced.
 No need of fatty acid activation & coenzyme A
 Hydroxylation occurs at α-carbon atom.

29.  It is then oxidized to α-keto acid.
This, keto acid undergoes decarboxylation, yielding a molecule
of CO2 & FA with one carbon atom less.
 Occurs in endoplasmic reticulum.
 Some FA undergo α - oxidation in peroxisomes.

30.  α- oxidation is mainly used for fatty acids that have a methyl
group at the beta-carbon, which blocks beta- oxidation.
Major dietary methylated fatty acid is phytanic acid.
 It is derived from phytol present in chlorophyll, milk & animal
fats.

31. Omega oxidation
Minor pathway, takes place in microsomes.
Catalyzed by hydroxylase enzymes involving NADPH &
cytochrome P-450.
 Methyl (CH3) group is hydroxylated to CH2OH & subsequently
oxidized with the help of NAD+ to COOH group to produce
dicarboxylic acids.
 When β-oxidation is defective & dicarboxylic acids are
excreted in urine causing dicarboxylic aciduria.