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Chapter 18 Metabolic Pathways and
Energy Production
1
18.7
Oxidation of Fatty Acids
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
b Oxidation of Fatty Acids
2
In stage 2 of fat metabolism, fatty acids undergo beta
oxidation, which removes two carbon segments from
carbonyl end.
Each cycle in oxidation produces acetyl CoA and a fatty acid
that is shorter by two carbons.
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Fatty Acid Activation
3
Fatty acid activation
• prepares them for transport through the inner membrane of
mitochondria
• combines a fatty acid with coenzyme A to yield fatty
acyl CoA
• requires energy obtained from hydrolysis of ATP to give
AMP and 2Pis
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Reactions 1 and 2 of b-Oxidation Cycle
4
Reaction 1 Dehydrogenation
Hydrogen atoms removed by FAD from the α and β carbons
form a double bond and FADH2.
Reaction 2 Hydration
H−OH adds across the double bond, the −OH on the β
carbon.
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Reactions 1 and 2 of b-Oxidation Cycle
5
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Reaction 3 of b-Oxidation Cycle
6
Reaction 3 Oxidation
The −OH on the β carbon is oxidized by NAD+, forming a β
ketone and NADH + H+.
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Reactions 3 of b-Oxidation Cycle
7
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Reaction 4 of b-Oxidation Cycle
8
Reaction 4 Cleavage
The Cα—Cβ is cleaved to yield acetyl CoA and a shorter
(8C) fatty acyl CoA. The process is repeated until the
fatty acid is completely broken down.
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Reaction 4 of b-Oxidation Cycle
9
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Learning Check
10
Match the reactions of b oxidation with each.
oxidation 1
hydration
oxidation 2
fatty acyl CoA cleaved
A.
B.
C.
D.
E.
Water is added.
FADH2 forms.
A two-carbon unit is removed.
A hydroxyl group is oxidized.
NADH forms.
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Solution
11
Match the reactions of b oxidation with each.
oxidation 1
hydration
oxidation 2
fatty acyl CoA cleaved
A.
B.
C.
D.
E.
Water is added.
FADH2 forms.
A two-carbon unit is removed.
A hydroxyl group is oxidized.
NADH forms.
hydration
oxidation 1
fatty acyl CoA cleaved
oxidation 2
oxidation 2
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Cycles of b Oxidation
12
The number of b-oxidation cycles
• depends on the length of a fatty acid
• is one less than the number of acetyl CoA groups formed
b-Oxidation
Carbons in
Fatty Acid
Acetyl CoA
(C/2)
Cycles (C/2−1)
14
7
6
16
8
7
18
9
8
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
ATP from Fatty Acid Oxidation
13
In each b-oxidation cycle,
• 1 NADH is produced, generating 3 ATPs
• 1 FADH2 is produced, generating 2 ATPs
• 1 acetyl CoA is produced, generating 12 ATPs
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
ATP from β Oxidation of Myristic Acid
14
ATP Production from β Oxidation for Myristic Acid (14C)
Source
Activation
7 acetyl CoA
ATPs
−2 ATP
(14 C atoms x 1 acetyl CoA/2 C atoms)
7 acetyl CoA x 12 ATPs/acetyl CoA
6 β-oxidation cycles (coenzymes)
6 FADH2 x 2 ATP/FADH2
6 NADH x 3 ATP/NADH
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
84 ATP
12 ATP
18 ATP
Total 112 ATP
Copyright © 2012 by Pearson Education, Inc.
Learning Check
15
1. The number of acetyl CoA groups produced by the complete
b oxidation of palmitic acid (C16) is
A. 16
B. 8
C. 7
2. The number of oxidation cycles to completely oxidize
palmitic acid (C16) is
A. 16
B. 8
C. 7
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Solution
16
1. The number of acetyl CoA groups produced by the complete
b oxidation of palmitic acid (C16) is
The answer is B. 8.
2. The number of oxidation cycles to completely oxidize
palmitic acid (C16) is
The answer is C. 7.
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Oxidation of Unsaturated Fatty Acids
17
Many of the fats in our diets, especially the oils, contain
unsaturated fatty acids, which have one or more double bonds.
Since unsaturated fats are ready for hydration,
• no FADH2 is formed in this step
• the energy from β oxidation is slightly less
• for simplicity, we will assume that the total ATP production is
the same for saturated and unsaturated fatty acids
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Ketone Bodies
18
If carbohydrates
are not available,
• body fat breaks
down to meet
energy needs
• compounds called
ketone bodies form
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Formation of Ketone Bodies
19
Ketone bodies form
• if large amounts of acetyl CoA accumulate
• when two acetyl CoA molecules form acetoacetyl CoA
• when acetoacetyl CoA hydrolyzes to acetoacetate
• when acetoacetate reduces to b-hydroxybutyrate or loses
CO2 to form acetone, both ketone bodies
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Ketosis
20
Ketosis occurs
• in diabetes, diets high in
fat, and starvation
• as ketone bodies
accumulate
• when acidic ketone
bodies lower blood pH
below 7.4 (acidosis)
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Fatty Acid Synthesis from
Carbohydrates
21
When the body has met all its energy needs and the glycogen
stores are full, excess acetyl CoA from the breakdown of
carbohydrates is used to form new fatty acids.
In this process,
• two-carbon acetyl units are linked to give new fatty acids
• undergo synthesis reactions that are the reverse of the βoxidation reactions
• the synthesis occurs in the cytosol instead of the mitochondria
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.
Fatty Acid Synthesis from
Carbohydrates
22
In diabetes,
• insulin does not function properly
• glucose levels are insufficient for
energy needs
• fats are broken down to acetyl CoA
• ketone bodies form
Chemistry: An Introduction to General, Organic, and Biological Chemistry, Eleventh Edition
Copyright © 2012 by Pearson Education, Inc.