LIPID METABOLISM

1. Classification of lipids
2. Hydrolysis of triglycerids
3. Oxidation of fatty acids
4. Biosynthesis of fatty acids
CLASSIFICATION OF LIPIDS
FUNCTIONS OF LIPIDS
 Fatty Acids

CH3(CH2)nCH2CO2H

O O
CH3(CH2)nCH2C-OH H-O-R CH3(CH2)nCH2C-OH H-S-R

O O
CH3(CH2)nCH2C-O-R CH3(CH2)nCH2C-S-R
Ester Thioester

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KATABOLISM OF LIPIDS
ANABOLISM OF LIPIDS (BIOSYNTHESIS)
Slide 6 of 95
Release of Fatty Acids from Triglycerids
O
CH2OC-R1 CH2OH
O Lipases
CHOC-R2 CHOH

O
CH2OC-R3 CH2OH
Triacylglycerol Glycerol
+
O O O
HOC-R1 HOC-R2 HOC-R3
Acylglycerol (Triglyceride) Lipases
Diacylglycerol (DAG)

Triacylglycerol
Lipase

OH
Triacylglycerol (TAG) Diacylglycerol
Lipase

OH OH
Monoacylglycerol
Lipase
OH

Monoacylglycerol
OH OH (MAG)

Glycerol

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GLYCEROL METABOLISM
 Fatty Acid Oxidation
Fatty acid degradation occurs in the mitochondria and yields acetyl CoA
and reduced cofactors via β-oxidation.

Subsequent oxidation of these products by the TCA (Krebs) cycle and the
electron transport pathway yields ATP.

Example: Palmitoyl CoA

+ CoA-SH Palmitoyl CoA

 Beta Oxidation

• Cleavage of fatty acids to acetate in tissues

• Occurs in mitochondria

[O] [O] [O] [O] [O] [O] [O] [O]

9 CH3COSCoA
CO2H

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 Steps in Beta Oxidation
• Fatty Acid Activation by Esterification with
CoASH
• Membrane Transport of Fatty Acyl CoA Esters
• Carbon Backbone Reaction Sequence
• Dehydrogenation
• Hydration
• Dehydrogenation
• Carbon-Carbon Cleavage (Thiolase Reaction)

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Fatty Acid Activation by Esterification with CoASH

AcylCoA

CoASH + RCO2H + ATP RCOSCoA + AMP + PPi

Synthetase Pyrophos-
phatase
Occurs in outer mitochondrial
membrane for long chain fatty acids 2 Pi

ATP AMP + PPi -32.3

CoASH + RCO2H RCOSCoA +31.5
PPi 2 Pi -33.6
G0’(KJ/mole)
-34.4
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Membrane Transport of Fatty Acyl CoA Esters

+ O
RCOSCoA +(CH3)3N
O-
OH
Carnitine Carnitine
Carnitine
acyltransferase II acyltransferase I
(matrix side of (outer part of mitochondrial
inner mitochondrial inner membrane)
membrane)

+ O
(CH3)3N
O-
O2CR

O-Acylcarnitine

Transported across inner mitochondrial

membrane by translocase

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 Translocase

Carnitine acyltransferase I Carnitine acyltransferase II

Source: http://cellbio.utmb.edu/cellbio/mitochondria_1.htm 23
 Beta Oxidation Reaction Sequence
Acyl CoA
HH Dehydrogenase H
R-CH2-C-C-COSCoA R-CH2-C=C-COSCoA
HH FAD FADH H - 2-enoyl CoA
trans
2
H2O
Enoyl CoA Hydratase
L--Hydroxyacyl
-Ketoacyl CoA
CoA HH
H Dehydrogenase
R-CH -C-C-COSCoA R-CH2-C-C-COSCoA
2

OH HO H L--Hydroxyacyl CoA
NADH NAD+
+ H+
CoASH
Thiolase

(-ketothiolase) Occurs in Mitochondria

R-CH2-C-SCoA CH3-C-SCoA
+
O O

Repeat Sequence
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 Complete Beta Oxidation of Palmitoyl CoA

CH3CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2COSCoA

7 Cycles

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Energetics of Complete Oxidation of Fatty Acids

High Energy Phosphate

Bonds Generated

Palmitic Acid Palmitoyl CoA -2

TCA Cycle
CH3COSCoA CO2 + H2O 108

Net 106
106 High Energy Phosphate Bonds G0’ = 3,233 KJ/Mole

For Palmitic Acid CO2: Efficiency

G0’ = - 9,790 KJ/Mole of -Oxidation = 33%

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 Beta Oxidation of Odd Carbon Fatty Acids

CH3CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2COSCoA

5 Cycles

5 CH3COSCoA + CH3CH2COSCoA
Propionyl CoA
Propionyl CoA Carboxylase
TCA Cycle ATP/CO2

CO2H CO2H
Mutase Epimerase

HO2CCH2CH2COSCoA CH3-C-H H-C-CH3

Succinyl CoA Vit. B12

COSCoA COSCoA
L-Methylmalonyl D-Methylmalonyl
CoA CoA
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 Beta Oxidation of Unsaturated Fatty Acids

H H
CH3(CH2)7-C=C-CH2(CH2)6COSCoA
Oleoyl CoA
Beta Oxidation
(3 Cycles)

H
H H Isomerase

CH3(CH2)7-C=C-CH2COSCoA CH3(CH2)7-CH2-C=C-COSCoA

cis-3 trans- 2 H

Continuation of Beta Oxidation

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 The Number of Cycles in β-Oxidation

The length of a fatty acid:

• Determines the number of oxidations and
• The total number of acetyl CoA groups.
Carbons in Acetyl CoA -Oxidation Cycles
Fatty Acid (C/2) (C/2 –1)
12 6 5
14 7 6
16 8 7
18 9 8
 Ketogenesis: Formation of Ketone Bodies

Thiolase
2 CH3COSCoA CH3COCH2COSCoA CH3COSCoA

Acetoacetyl CoA

HMG CoA
Synthase

Several
Cholesterol steps OH
(in cytosol)
HO2C-CH2-C-CH2COSCoA

CH3
(in liver: mitochon-
drial matrix) Ketogenesis -Hydroxy--methylglutaryl CoA
(HMG CoA)
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Ketogenesis: Formation of Ketone Bodies (Cont’d.)

OH
HMG CoA
HO2C-CH2-C-CH2COSCoA lyase
CH3COCH2CO2
CH3 - CH3COSCoA Acetoacetate
HMG CoA NADH + H+
Dehydrogenase - CO2
+
NAD

OH
CH3COCH3
CH3CHCH2CO2
Acetone
-Hydroxybutyrate (volatile)

Ketone bodies are important sources

of energy, especially in starvation
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 Ketone Bodies As Energy Sources
In liver

-Hydroxybutyrate Acetoacetate Succinyl CoA

Acetoacetate is major energy

source in cardiac muscle and
renal cortex; also in brain in -Ketoacyl CoA
starvation and diabetes transferase

Not found in liver

Thiolase
Succinate
2 Acetyl CoA Acetoacetyl CoA

Combines with
oxaloacetate

TCA Cycle
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OVERVIEW OF METABOLISM
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 Overview of Metabolism

In metabolism:
• Catabolic pathways degrade large molecules.
• Anabolic pathway synthesize molecules.
• Branch points determine which compounds are
degraded to acetyl CoA to meet energy needs or
converted to glycogen for storage.

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The End