Section 12 - Fatty Acid and Lipid Metabolism
Chapter 27 - Fatty Acid Degradation
● Fatty acids → stored as triacylglycerols in adipose tissue
27.1 - Fatty Acids Are Processed in Three Stages
● 3 stages of processing
○ Lipids must be mobilized
■ Lipolysis
■ Triacylglycerols are degraded to fatty acids and glycerol,
which are released from the adipose tissue and transported
to the energy-requiring tissues
○ Fatty acids must be activated and transported into
the mitochondria
○ Fatty acids are broken down into acetyl CoA
● Triacylglycerols are hydrolyzed by hormone-stimulated
lipases
● Free fatty acids and glycerol are released into the blood
○ Fatty acids bind to the blood protein albumin
○ Glycerol → absorbed by the liver → phosphorylated
→ oxidized to dihydroxyacetone phosphate →
isomerized to glyceraldehyde-3-phosphate
● Fatty acids are linked to Coenzyme A before they are oxidized
○ Fatty acids separate from albumin → diffuse across the cell membrane with
the assistance of transport proteins (shuttles)
○ Fatty acid oxidation takes place in the mitochondria
■ Fatty acids must be activated by reacting with acyl CoA
● Takes place on the outer mitochondrial membrane
● Catalyzed by acyl CoA synthetase
● 2 steps of activation
○ Fatty acid reacts with ATP to form an acyl adenylate
and
■ Fatty acid + ATP ⇌ acyl adenylate
○ The sulfhydryl group of CoA attacks the acyl adenylate
to form acyl CoA and AMP
■ Acyl adenylate + sulfhydryl group of CoA ⇌ acyl
CoA + AMP
● The reaction is driven forward by the hydrolysis of
pyrophosphate by pyrophosphatase
● Many biosynthetic reactions are made irreversible by the
hydrolysis of inorganic pyrophosphate
● Complete reaction
○ RCOO- + CoA + ATP + H2O → RCO-CoA + AMP + 2 Pi
, ■ Activated fatty acids cross the outer mitochondrial membrane through
voltage-dependent ion channels (porin channels)
■ Transport across the inner mitochondrial membrane requires the fatty
acids to be linked to carnitine
● Acyl group is transferred from the sulfur atom of CoA to the
hydroxyl group of carnitine → forms acyl carnitine
○ Catalyzed by carnitine acyltransferase I ( bound to the
outer mitochondrial membrane)
● Acyl carnitine shuttled across the inner membrane by a
translocase
● Acyl group is transferred back to CoA by carnitine
acyltransferase II (On the matrix side of the membrane
● Translocase returns carnitine to the cytoplasmic side in
exchange for an incoming acyl carnitine
● Acetyl CoA, NADH, and FADH2 are generated by fatty acid oxidation
○ The goal of fatty acid degradation: oxidize the fatty acid to acetyl CoA and
gather high-energy electrons to power oxidative phosphorylation
○ Saturated acyl CoA is degraded by a recurring sequence of 4 reactions
■ Oxidation by flavin adenine dinucleotide (FAD)
■ Hydration
■ Oxidation by nicotinamide adenine dinucleotide (NAD+)
■ Thiolysis by coenzyme A
○ Result of these reactions: fatty acid chain is shortened by 2 carbon atoms,
FADH2, NADH, and acetyl CoA are generated
○ Because oxidation takes place at the β-carbon atom → β-oxidation pathway
■ First reaction → oxidation of acyl CoA by acyl CoA dehydrogenase
● Gives an enoyl CoA with a trans double bond between C-2 and
C-3
● Acyl CoA + E-FAD → trans- Δ2-enoyl CoA + E-FADH2
● Electron acceptor: FAD
■ Second step → hydration of the double bond between C-2 and C-3 by
enoyl CoA hydratase
● trans-Δ2-enoyl CoA + H2O ⇌ L-3-hydroxyacyl CoA
● Hydration is stereospecific
■ Third step → oxidation of the hydroxyl group at C-3 into a keto group
● Generated NADH
● Catalyzed by L-3-hydroxyacyl CoA dehydrogenase
● L-3-hydroxyacyl CoA + NAD+ ⇌ 3-ketoacyl CoA + NADH + H+
■ Final step → cleavage of 3-ketoacyl CoA by the thiol group of a
second molecule of coenzyme A
● Yields acetyl Coa and an acyl CoA shortened by 2 carbon
atoms
● Catalyzed by β-ketothiolase
● 3-ketoacyl CoA + HS-CoA → acetyl CoA + acyl CoA
(n C atoms) (n-2 C atoms)
Chapter 27 - Fatty Acid Degradation
● Fatty acids → stored as triacylglycerols in adipose tissue
27.1 - Fatty Acids Are Processed in Three Stages
● 3 stages of processing
○ Lipids must be mobilized
■ Lipolysis
■ Triacylglycerols are degraded to fatty acids and glycerol,
which are released from the adipose tissue and transported
to the energy-requiring tissues
○ Fatty acids must be activated and transported into
the mitochondria
○ Fatty acids are broken down into acetyl CoA
● Triacylglycerols are hydrolyzed by hormone-stimulated
lipases
● Free fatty acids and glycerol are released into the blood
○ Fatty acids bind to the blood protein albumin
○ Glycerol → absorbed by the liver → phosphorylated
→ oxidized to dihydroxyacetone phosphate →
isomerized to glyceraldehyde-3-phosphate
● Fatty acids are linked to Coenzyme A before they are oxidized
○ Fatty acids separate from albumin → diffuse across the cell membrane with
the assistance of transport proteins (shuttles)
○ Fatty acid oxidation takes place in the mitochondria
■ Fatty acids must be activated by reacting with acyl CoA
● Takes place on the outer mitochondrial membrane
● Catalyzed by acyl CoA synthetase
● 2 steps of activation
○ Fatty acid reacts with ATP to form an acyl adenylate
and
■ Fatty acid + ATP ⇌ acyl adenylate
○ The sulfhydryl group of CoA attacks the acyl adenylate
to form acyl CoA and AMP
■ Acyl adenylate + sulfhydryl group of CoA ⇌ acyl
CoA + AMP
● The reaction is driven forward by the hydrolysis of
pyrophosphate by pyrophosphatase
● Many biosynthetic reactions are made irreversible by the
hydrolysis of inorganic pyrophosphate
● Complete reaction
○ RCOO- + CoA + ATP + H2O → RCO-CoA + AMP + 2 Pi
, ■ Activated fatty acids cross the outer mitochondrial membrane through
voltage-dependent ion channels (porin channels)
■ Transport across the inner mitochondrial membrane requires the fatty
acids to be linked to carnitine
● Acyl group is transferred from the sulfur atom of CoA to the
hydroxyl group of carnitine → forms acyl carnitine
○ Catalyzed by carnitine acyltransferase I ( bound to the
outer mitochondrial membrane)
● Acyl carnitine shuttled across the inner membrane by a
translocase
● Acyl group is transferred back to CoA by carnitine
acyltransferase II (On the matrix side of the membrane
● Translocase returns carnitine to the cytoplasmic side in
exchange for an incoming acyl carnitine
● Acetyl CoA, NADH, and FADH2 are generated by fatty acid oxidation
○ The goal of fatty acid degradation: oxidize the fatty acid to acetyl CoA and
gather high-energy electrons to power oxidative phosphorylation
○ Saturated acyl CoA is degraded by a recurring sequence of 4 reactions
■ Oxidation by flavin adenine dinucleotide (FAD)
■ Hydration
■ Oxidation by nicotinamide adenine dinucleotide (NAD+)
■ Thiolysis by coenzyme A
○ Result of these reactions: fatty acid chain is shortened by 2 carbon atoms,
FADH2, NADH, and acetyl CoA are generated
○ Because oxidation takes place at the β-carbon atom → β-oxidation pathway
■ First reaction → oxidation of acyl CoA by acyl CoA dehydrogenase
● Gives an enoyl CoA with a trans double bond between C-2 and
C-3
● Acyl CoA + E-FAD → trans- Δ2-enoyl CoA + E-FADH2
● Electron acceptor: FAD
■ Second step → hydration of the double bond between C-2 and C-3 by
enoyl CoA hydratase
● trans-Δ2-enoyl CoA + H2O ⇌ L-3-hydroxyacyl CoA
● Hydration is stereospecific
■ Third step → oxidation of the hydroxyl group at C-3 into a keto group
● Generated NADH
● Catalyzed by L-3-hydroxyacyl CoA dehydrogenase
● L-3-hydroxyacyl CoA + NAD+ ⇌ 3-ketoacyl CoA + NADH + H+
■ Final step → cleavage of 3-ketoacyl CoA by the thiol group of a
second molecule of coenzyme A
● Yields acetyl Coa and an acyl CoA shortened by 2 carbon
atoms
● Catalyzed by β-ketothiolase
● 3-ketoacyl CoA + HS-CoA → acetyl CoA + acyl CoA
(n C atoms) (n-2 C atoms)
