Download Synthesis of Fatty Acids

24.5 Fatty Acid Synthesis
When the body has met all its energy needs and the glycogen
stores are full,
• acetyl CoA from the breakdown of carbohydrates and fatty
acids is used to synthesize new fatty acids in the cytosol.
• two-carbon acetyl units are linked to form a 16-carbon fatty
acid, palmitic acid, in the pathway called lipogenesis.
Learning Goal Describe the biosynthesis of fatty acids
from acetyl CoA.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Lipogenesis: Fatty Acid Synthesis
The synthesis of fatty acids
• proceeds in a separate pathway, with different enzymes; it
is not a simple reversal of fatty acid oxidation.
• occurs in the cytosol using the reduced coenzyme NADPH
instead of occurring in the mitochondria, where oxidation
takes place using FAD and NAD+.
The reduced coenzyme NADPH is similar to that of NADH,
with a phosphate group.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Synthesis, Acyl Carrier Protein, ACP
In fatty acid synthesis,
• an acyl carrier protein (HS — ACP) activates the
acyl compounds.
• HS — ACP contains the thiol and pantothenic acid
(vitamin B5) groups found in acetyl CoA attached to
a protein.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Preparation of Activated Carriers
Before fatty acid synthesis can begin, the activated carriers
must be synthesized.
The synthesis of a three-carbon malonyl ACP requires
• the synthesis of malonyl CoA, when acetyl CoA combines
with bicarbonate.
• the hydrolysis of ATP, which provides the energy for the
reaction.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Preparation of Activated Carriers
The activated forms of malonyl ACP and acetyl ACP are
produced when the acyl group is combined with HS — ACP.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Synthesis of Fatty Acids: Reaction 1
The synthesis of a fatty acid
occurs in the cytosol and
requires a cycle of four
reactions:
In reaction 1, condensation,
• 3-ketoacyl ACP synthase
catalyzes the condensation
of acetyl ACP and
malonyl ACP.
• a four-carbon acetoacetyl
ACP and CO2 are
produced.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Synthesis of Fatty Acids: Reaction 2
In reaction 2, reduction,
• 3-ketoacyl ACP reductase
reduces the 3-keto group
using 2H from
NADPH + H+.
• 3-hydroxyacyl ACP, an
alcohol, and the oxidized
coenzyme NADP+ are
produced.
In the cytosol, NADPH is
used to provide hydrogen for
reduction reactions.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Synthesis of Fatty Acids: Reaction 3
In reaction 3, dehydration,
• 3-hydroxyacyl ACP
dehydrase catalyzes the
dehydration of the
hydroxyl.
• a trans double bond in
trans-2-enoyl ACP is
formed.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Synthesis of Fatty Acids: Reaction 4
In reaction 4, reduction,
• enoyl ACP reductase uses
hydrogen from NADPH +
H+ to reduce the double
bond to a single bond.
• butyryl ACP, a saturated
four-carbon compound,
two carbon atoms longer
than the original acetyl
ACP, forms.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Fatty Acid Synthesis, Cycle Repeats
The cycle of fatty acid synthesis
repeats as
• malonyl-ACP combines with
the four-carbon butyryl-ACP
to form six-carbon
hexanoyl-ACP.
• C16 palmitoyl ACP, is
hydrolyzed to yield palmitate
and HS — ACP after
seven cycles.
The overall equation for the
synthesis of palmitate from
acetyl CoA is written as follows:
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Longer and Shorter Fatty Acids
Palmitate is the first fatty acid produced by fatty acid
synthesis.
However,
• shorter fatty acids are released earlier in the fatty acid
synthesis process before there are 16 carbon atoms in
the chain.
• longer fatty acids are produced with special enzymes that
add two-carbon acetyl units to the carboxyl end of the fatty
acid chain.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Regulation of Fatty Acid Synthesis
Fatty acid synthesis occurs in the adipose tissue and is
stimulated by insulin. When blood glucose is high, insulin
• moves glucose into the cells, stimulating glycolysis and the
oxidation of pyruvate.
• produces acetyl CoA for fatty acid synthesis.
Two carbons are added to the growing fatty acid chain by
using three-carbon malonyl units.
The transport of acyl groups into the matrix of the
mitochondria is blocked, preventing their oxidation.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Summary of Lipogenesis
In fatty acid synthesis (lipogenesis2),
two-carbon units from acetyl CoA are
added together to form palmitate.
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Comparing β Oxidation and Fatty Acid
Synthesis
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Study Check
Match each with the description below.
1) Mitochondria
2) cytosol
3) glucagon
4) Insulin
5) acetyl ACP
6) malonyl ACP
A.
B.
C.
D.
E.
F.
site of fatty acid synthesis
site of β oxidation
starting material for lipogenesis
compound added to elongate acyl-ACP
activates β oxidation
activates lipogenesis
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
© 2016 Pearson Education, Inc.
Solution
Match each with the description below.
1) Mitochondria
2) cytosol
3) glucagon
4) Insulin
5) acetyl ACP
6) malonyl ACP
A. site of fatty acid synthesis
B. site of β oxidation
C. starting material for lipogenesis
D. compound added to elongate acyl-ACP
E. activates β oxidation
F. activates lipogenesis
General, Organic, and Biological Chemistry: Structures of Life, 5/e
Karen C. Timberlake
2) cytosol
1) mitochondria
5) acetyl ACP,
6) malonyl ACP
6) malonyl ACP
3) glucagon
4) insulin
© 2016 Pearson Education, Inc.