Lipids &Fatty Acids

Metaboilsm
Asist prof. Dr. Alaa Kamal Jabbar
Alhamd
M Sc. & Ph. D. In Clinical
Biochemistry
Ph D. Course-Biology
Department of Chemistry
College of Sciences\ University of
Almustansirya
2017-2018
1. 1..Lehninger Principle of Biochemistry , David Nelson , 4th
Edition (2008).
2. Biochemistry , Lubbert Steryer,6th edition (2006).
3. Harpers Illustrated Biochemistry , Robbert Murray, 26 th
edition (2003).
4. The Chemical basis of Life , George Schimd , 2th edition
(1985).
Lipid Metabolism

Fatty Acid Metabolism

Fatty acids play several important roles:

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Introduction
 Overview of fatty
acid synthesis

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Triglycerides
Triglycerides are a highly concentrated store of
energy
9 kcal/g vs 4 kcal/g for glycogen
Glycogen is also highly hydrated, 2 g H2O/g
glycogen

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Pancreatic Lipases
Dietary triacylglycerols must be broken down before being
absorbed by the intestines.
Bile salts, which act as detergents, are used to solublize the
triacylglycerols

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Utilization of Fatty Acids as Fuel
Three stages of processing

Triglycerols are degraded to fatty acids and glycerol in

Fatty acids are activated and transported into the

Fatty acids are broken down into two-carbon acetyl–

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Degrdation of Triacylglycerols
In the adipose tissue, lipases are activated by hormone
signaled phosphorylation

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The lipases break the
triacylglycerols down to
fatty acids and glycerol
The fatty acids are
transportred in the blood
by serum albumin

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The glycerol is absorbed by the liver and converted to
glycolytic intermediates.

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Activation of Fatty Acids
 Acyl CoA synthetase reaction occurs in the on the
mitochondrial membrane

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Transport into Mitochondrial Matrix
Cantina carries
long-chain activated
fatty acids into the
mitochondrial matrix
Transport into Mitochondrial Matrix
Carnitine carries long-chain activated fatty acids into
the mitochondrial matrix

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Fatty acid oxidation
Each round in fatty acid
degradation involves four
reactions
1. oxidation to
trans-∆2-Enoly-CoA

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Fatty acid oxidation
 Each round in fatty acid
degradation involves four
reactions
 2. Hydration to L–3–
Hydroxylacyl CoA

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Each round in fatty acid
degradation involves four
reactions
3. Oxidation to
3–Ketoacyl CoA

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Each round in fatty acid
degradation involves four
reactions
4. Thiolysis to produce
Acetyl–CoA

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Each round in fatty acid
degradation involves four
reactions
The process repeats itself

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Each round in fatty acid degradation involves four
reactions

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ATP Yield
The complete oxidation of the sixteen carbon palmitoyl–
CoA produces 106 ATP's

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Special Cases
Unsaturated fatty acids
(monounsaturated)

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Unsaturated fatty acids (polyunsaturated)

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Odd-Chain

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Ketone Bodies
Use of fatty acids in the citric acid cycle requires
carbohydrates for the the production of oxaloacetate.
During starvation or diabetes, OAA is used to make glucose
Fatty acids are then used to make ketone bodies
(acetoacetate and D–3–hydroxybutarate)

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Ketone bodies, acetoacetate and 3–hydroxybutarate are
formed from Acetyl–CoA .

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Ketone Bodies as a Fuel Source
The liver is the major source of ketone bodies.
It is transported in the blood to other tissues
Acetoacetate in the tissues
Acetoacetate is first activated to acetoacetate by
transferring the CoASH from succinyl–CoA.
It is then split into two Acetyl–CoA by a thiolase
reaction

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Fatty Acids Cannot be Used to
Synthesize Glucose
Even though the citric acid cycle intermediate
oxaloacetate can be used to synthesize glucose, Acetyl–
CoA cannot be used to synthesize oxaloacetate.
The two carbons that enter the citric acid cycle as
Acetyl–CoA leave as CO2.

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Fatty Acid Synthesis
Fatty acid are synthesized and degraded by different
pathways.
Synthesis takes place in the cytosol.
Intermediates are attached to the acyl carrier protein
(ACP).
In higher organisms, the active sites for the synthesis
reactions are all on the same polypeptide.
The activated donor in the synthesis is malonyl–ACP.
Fatty acid reduction uses NADPH + H+.
Elongation stops at C16 (palmitic acid)

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Formation of Malonyl Coenzyme A
Formation of malonyl–CoA is the committed step in fatty
acid synthesis.
Acryl Carrier Protein
The intermediates in fatty acid synthesis are covalently linked
to the acyl carrier protein (ACP)
Elongation
In bacteria the enzymes that are involved in elongation are
separate proteins; in higher organisms the activities all reside
on the same polypeptide.
To start an elongation cycle, Acetyl–CoA and Malonyl–
CoA are each transferred to an acyl carrier protein

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Acyl-malonyl ACP
condensing enzyme
forms Acetoacetyl-ACP.

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The next three reactions are similar to the reverse of fatty
acid degradation, except
The NADPH is used instead of NADH and FADH2
The D–enantiomer of Hydroxybutarate is formed
instead of the L–enantiomer

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The elongation cycle is repeated six more times, using
malonyl–CoA each time, to produce palmityl–ACP.

A thioesterase then cleaves the palmityl–CoA from the

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Stoichiometry of FA synthesis
The stoichiometry of palmitate synthesis:
Synythesis of palmitate from Malonyl–CoA

Synthesis of Malonyl–CoA from Acetyl–CoA

Overall synthesis

Acetyl–CoA is synthesized in the mitochondrial matrix,

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Sources of NADPH
The malate dehydrogenase and NADP+–linked malate
enzyme reactions of the citrate shuttle exchange NADH for
NADPH
Regulation of Fatty Acid Synthesis
Regulation of Acetyl carboxylase
Global
+ insulin
- glucagon
- epinephrine
Local
+ Citrate
- Palmitoyl–CoA
- AMP
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Elongation and Unsaturation
Endoplasmic reticulum systems introduce double bonds
into long chain acyl–CoA's
Reaction combines both NADH and the acyl–CoA's to
reduce O2 to H2O.
Elongation and unsaturation convert palmitoyl–CoA to
other fatty acids.
Reactions occur on the cytosolic face of the
endoplasmic reticulum.
Malonyl–CoA is the donor in elongation reactions

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