1. 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.

2. 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.

3. 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.

4. 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.

5. Preparation of Activated Carriers
The activated forms of malonyl ACP and acetyl ACP are produced when the acyl group is combined with HS — ACP.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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:

11. 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.

12. 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.

13. Summary of Lipogenesis
In fatty acid synthesis (lipogenesis2), two-carbon units from acetyl CoA are added together to form palmitate.

14. Comparing β Oxidation and Fatty Acid Synthesis

15. Study Check
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

16. 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
starting material for lipogenesis
D. compound added to elongate acyl-ACP
E. activates β oxidation
F. activates lipogenesis
2) cytosol
1) mitochondria
5) acetyl ACP,
6) malonyl ACP
3) glucagon
4) insulin