Biosynthesis and

oxidation of fatty
acids
METABOLISME

Leerjaar 2: Algemene fase HLO

Fatty acid oxidation provides

metabolic energy, heat, and water
4

Lipogenesis
5

Biosynthesis of fatty acids by a two

enzyme system:

Location:

Acetyl CoA carboxylase

Fatty acid synthase

Cytosol

Many Tissues: including liver, kidney, brain,

lung, mammary gland, and adipose tissue.

Formation of malonyl-CoA
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Acetyl-CoA carboxylase

Two step reaction:

carboxylation of biotin involving
ATP and HCO3 transfer of the carboxyl to
acetyl-CoA to form malonylCoA.
Acetyl-CoA
carboxylase

Fas: condensation &

reduction

Fas: dehydration &

reduction

Continued
synthesis
The sequence of reactions is repeated six
more times until a saturated 16-carbon acyl
radical (palmityl) has been assembled

The free palmitate must be activated to

acyl-CoA before it can proceed via any
other metabolic pathways.

Citrate transporter
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Overall synthesis reaction

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Acetyl-CoA + 7 malonyl-CoA + 14NADPH +

14H+
Palmitate + 7CO2 + 14NADP+ + 8
HSCoA + 6H2O

7 Acetyl-CoA + 7CO2 + 7ATP

7 malonyl-CoA +7ADP + 7Pi + 7H+

8 Acetyl-CoA + 14 NADPH + 7H+ + 7ATP

Palmitate + 14 NADP+ + 8 HSCoA + 6H2O + 7ADP + 7Pi

Regulation of lipogenesis
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Essential Fatty Acids

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Linoleic acid
-linolenic acid

Used for eicosanoids synthesis

Greek Eikosi: twenty
Polyunsaturated
Local hormones

Eicosanoids
14

Cyclooxygenase pathway

Thromboxanes: cause vasoconstriction &

platelet aggregation
Prostacyclins: inhibit platelet aggregation
Prostaglandins: mediate fever, pain,
inflammation, gastrointestinal protection

Lipoxygenase pathway

Leukotrienes: cause constriction of

bronchioles, vascular permeability, mediate
inflammation response
Lipoxins: are vasoactive and have a
immunoregulatory function

-oxidation of fatty acids

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Successive removal of acetyl-CoA

units

Location:

mitochondria

Fatty acid oxidation

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Activation of fatty acid

17

Carnitine shuttle
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-oxidation palmityl-CoA
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Oxidation of odd-chain FA
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The propionyl residue from an odd-chain

FA is the only part that is glucogenic

Electron transfer
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-oxidation in peroxisomes
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A modified form of -oxidation for the

oxidation of long chain fatty acids and
leads to the formation of acetyl-CoA
and H2O2 which is broken down by
catalase

ATP yield from -oxidation palmityl-CoA

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Regulation of oxidation
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Ketogenesis
25

Transport of ketone bodies

26

Regulation ketogenesis
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Steps in regulation of
ketogenesis

Ketosis only occurs in vivo if there is an

increase in the level of circulating free fatty
acids

After uptake by the liver, free fatty acids are

either oxidized to CO2 or ketone bodies or
esterified to triacylglycerol and phospholipid

Acetyl-CoA formed in -oxidation is oxidized in

the citric acid cycle, or it enters the pathway
of ketogenesis to form ketone bodies

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Starvation, Diabetes and

ketosis

glucose in cells malonyl-coA

production
inhibition of carnitine acyltransferase I
relieved
fatty acids enter mitochondria to be
degraded to acetyl-CoA
accumulation of acetyl-CoA accelerates
the formation of ketone bodies
increased blood levels of acetoacetate
and -hydroxybutyrate lower the blood

Degradation vs synthesis
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Questions???

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References
34

Harpers Illustrated biochemistry,

Lehninger Principles of Biochemistry,

26th
Edition by Murray, Mayes, Granner and Rodwell,
2003.

4th Edition by Nelson & Cox, 2005.