Transcript Fatty Acid Activation Fatty acid activation

LIPID
METABOLISM
Why Fatty Acids?
(For energy storage?)
• Two reasons:
– The carbon in fatty acids (mostly CH2) is almost
completely reduced (so its oxidation yields the
most energy possible).
– Fatty acids are not hydrated (as mono- and
polysaccharides are), so they can pack more
closely in storage tissues
Naming of fatty acids
C18
 
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9
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CH3-(CH2)7-CH=CH-CH2-CH2-CH2-CH2-CH2-CH2-CH2-COOH
Cis 9
18:0, stearic acid :
18:1 (9), oleic acid :
octadecanoic acid
octadecenoic acid
18:2 (9,12), linoleic acid :
octadecadienoic acid
18:3 (9,12,15), -linolenic acid :
octadecatrienoic acid
LIPID Metabolism
The body fat is our major source of
stored energy.
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Our adipose tissue is made of
fat cells adipocytes.
A typical 70 kg (150 lb) person
has about 135,000 kcal of
energy stored as fat, 24,000
kcal as protein, 720 kcal as
glycogen reserves, and 80 kcal
as blood glucose.
The energy available from
stored fats is about 85 % of the
total energy available in the
body.
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Digestion of Triacylglycerols
In the digestion of fats (triacylglycerols):
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Bile salts break fat globules into micelles in the small intestine.
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Pancreatic lipases hydrolyze ester bonds to form
monoacylglycerols and fatty acids, which recombine in the
intestinal lining.
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Lipoproteins form and transport triacylglycerols to the cells of
the heart, muscle, and adipose tissues.
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Brain and red blood cells cannot utilize fatty acids, because
fatty acids cannot diffuse across the blood-brain barrier, and
red blood cells have no mitochondria, where fatty acids are
oxidized. (Glucose and glycogen are the only source of energy
for the brain and red blood cells.)
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SOURCE OF FAT / fatty acids :
 Food
 Biosinthesis de novo
 Body reserve  adiposit
Fatty acids  be emulsified by
gall bladder salts – easy to
absorb and digest
Transport  complex with
protein  lipoprotein
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Penyerapan oleh sel
mukosa usus halus
Asam lemak yg diserap 
disintesis kembali mjd
lemak dalam  badan
golgi dan retikulum
endoplasma sel mukosa
usus halus
TAG  masuk ke sistem
limfa membentuk
kompleks dgn protein 
chylomicrons
Digestion of Triacylglycerols
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Fat Mobilization
Fat mobilization:
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Breaks down triacylglycerols in adipose
tissue to fatty acids and glycerol.
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Occurs when hormones glucagon and
epinephrine are secreted into the
bloodstream and bind to the receptors
on the membrane of adipose cells
activating the enzymes within the fat
cells that begin the hydrolysis of
triacylglycerols.
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Fatty acids are hydrolyzed initially from
C1 or C3 of the fat.
Lipases
Triacylglycerols +3H2O→Glycerol + 3Fatty acids
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Metabolism of Glycerol.
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Using two steps, enzymes in the liver convert
glycerol to dihydroxyacetone phosphate, which
is an intermediate in several metabolic pathways
including glycolysis and gluconeogenesis.
st
 1 step: glycerol is phosphorylated using ATP
to yield glycerol-3-phosphate.
nd step: the hydroxyl group is oxidized to yield
 2
dihydroxyacetone phosphate.
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The overall reaction :
Glycerol + ATP + NAD+ → Dihydroxyacetone
phosphate + ADP + NADH + H+
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Glycerol from TAG hydrolysis will be converse to
DHAP by :
1 Glycerol Kinase
2 Glycerol Phosphate Dehydrogenase.
Fatty Acid Activation
Fatty acid activation:
 Allows the fatty acids in the cytosol to enter the
mitochondria for oxidation.
 Combines a fatty acid with CoA to yield fatty
acyl CoA that combines with carnitine.
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Fatty Acid Activation
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Fatty acyl-carnitine transports the fatty acid
into the matrix.
The fatty acid acyl group recombines with
CoA for oxidation.
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Fatty Acid Activation
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Fatty acid activation is complex, but it
regulates the degradation and synthesis of
fatty acids.
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Beta-Oxidation of Fatty Acids
In reaction 1, oxidation:
 Removes H atoms from
the  and  carbons.
 Forms a trans C=C bond.
 Reduces FAD to FADH2.
 
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Beta-Oxidation of Fatty Acids
In reaction 2, hydration:
 Adds water across the
trans C=C bond.
 Forms a hydroxyl
group (—OH) on the 
carbon.
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Beta ()-Oxidation of Fatty Acids
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In reaction 3, a
second oxidation:
Oxidizes the hydroxyl
group.
Forms a keto group
on the  carbon.

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Beta ()-Oxidation of Fatty Acids
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In Reaction 4, acetyl
CoA is cleaved:
By splitting the bond
between the  and 
carbons.
To form a shortened
fatty acyl CoA that
repeats steps 1 - 4 of
-oxidation.
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Beta ()-Oxidation of Myristic (C14)
Acid
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Beta ()-Oxidation of Myristic (C14)
Acid (continued)
6 cycles
7 Acetyl
CoA
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Cycles of -Oxidation
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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)
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6
5
14
7
6
16
8
7
18
9
8
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-Oxidation and ATP
Activation of a fatty acid requires:
 2 ATP
One cycle of oxidation of a fatty acid produces:
 1 NADH
3 ATP
 1 FADH2
2 ATP
Acetyl CoA entering the citric acid cycle produces:
 1 Acetyl CoA
12 ATP
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ATP for Lauric Acid C12
ATP production for lauric acid (12 carbons):
Activation of lauric acid
-2 ATP
6 Acetyl CoA
6 acetyl CoA x 12 ATP/acetyl CoA
72 ATP
5 Oxidation cycles
5 NADH x 3ATP/NADH
15 ATP
5 FADH2 x 2ATP/FADH2
10 ATP
Total
95 ATP
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Oxidation of Unsaturated Fatty
Acids.
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Oxidation of monounsaturated fatty acyl-CoA
requires additional reaction performed with the
help of the enzyme isomerase.
Double bonds in the unsaturated fatty acids are in
the cis configuration and cannot be acted upon by
enoyl-CoA hydratase (the enzyme catalyzing the
addition of water to the trans double bond
generated during β-oxidation.
Enoyl-CoA isomerase repositions the double
bond, converting the cis isomer to trans isomer, a
normal intermediate in β-oxidation.
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Oxidation of polyunsaturated fatty
acids.
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Requires two additional reactions and a
second enzyme, reductase, in addition to
isomerase.
NADPH-dependent 2,4-dienoyl-CoA
reductase converts trans-2, cis-4-dienoylCoA intermediate into the trans-2-enoylCoA substrate necessary for β-oxidation.
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Oxidation of odd-chain fatty acids.
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Odd-carbon fatty acids are oxidized by the same pathway as evencarbon acids until three-carbon propionyl-CoA is formed.
After that, three additional reactions are required involving three
enzymes.
Propionyl-CoA is carboxylated by propionyl-CoA carboxylase (with
the cofactor biotin) to form the D stereoisomer of methylmalonylCoA (The formation of the carboxybiotin intermediate requires energy
from ATP).
D-methylmalonyl-CoA is changed into L-methylmalonyl-CoA by
methylmalonyl-CoA epimerase.
L-methylmalonyl-CoA undergoes an intramolecular rearrangment to
form succinyl-CoA, which enters the citric acid cycle. This
rearrangment is catalyzed by methylmalonyl-CoA mutase, which
requires coenzyme B12, derived from vitamin B12 (cobalamin).
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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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