Biochemistry: A Short Course: Fatty Acid Degradation

Tymoczko • Berg • Stryer
Biochemistry: A Short Course
CHAPTER 27
Fatty Acid Degradation
Triacylglycerols
(fats or triglycerides)
Three fatty acids

ester-linked to a
glycerol molecule
Used as energy storage

molecules in eukaryotes
Stored in adipocytes
Advantages of using triacylglycerols for energy storage
1. Fats are highly reduced hydrocarbons with a large energy
of oxidation.
2. Fats are insoluble molecules that aggregate into droplets.
They are unsolvated and no storage mass is water.
3. Fats are chemically inert. They can be stored without fear
of unfavorable reactions.
Disadvantages of triacylglycerols as energy storage

1. Fats must be emulsified before enzymes can digest them.
2. Fats are insoluble in the blood and must be carried in the
blood as protein complexes.
Dietary Lipid (Triacylglycerol) Metabolism
- In the small intestine, fat particles are coated with bile salts
and digested by pancreatic lipases
Two amphipathic bile salts that are cholesterol derivatives

Lipoproteins
Lipoproteins are large complexes of lipids and proteins designed to
transport lipids in the blood. The lipoproteins are classified
by particle density.
1. Chylomicrons (transport dietary cholesterol to tissues)

2. Very low density lipoprotein (VLDL) transport cholesterol
3. Intermediate density lipoprotein (IDL) produced by the liver to
4. Low density lipoprotein (LDL) tissues
5. High density lipoprotein (HDL) (transport cholesterol from tissues to liver)
Molecular Structure of a Chylomicron
Lipid degradation
Dietary lipids are hydrolyzed by lipases in three

steps to yield fatty acids and glycerol.
The fatty acids are taken up by cells and used

as a fuel.
Glycerol also enters the liver, where it can be

metabolized by the glycolytic or
gluconeogenic pathways.
Epinephrine and
glucagon stimulate
breakdown of
triacylglycerols
stored in adipocytes.
Protein kinase A
phosphorylates perilipin
and hormone-sensitive
lipase.
Phosphorylated perilipin activates

adipocyte triacylglyceride lipase
(ATGL), which breaks down lipids.
Upon entering the cell cytoplasm, fatty acids are activated by attachment to coenzyme A,
catalyzed by the enzyme acyl-CoA synthetase, costing two ATP equivalents.
After being activated by linkage to CoA, the fatty acid is transferred to carnitine, a
reaction catalyzed by carnitine acyltransferase I, for transport into the mitochondria.
A translocase transports the acyl carnitine into the mitochondria.
In the mitochondrial matrix, carnitine acyltransferase II transfers the fatty acid to CoA.
The fatty acyl CoA is now ready to be degraded.
In the mitochondria, carnitine acyltransferase II transfers the fatty acid to CoA.
The fatty acyl CoA is now ready to be degraded in the mitochondria by β-oxidation.
Beta Oxidation of Fatty Acids
1 2
Repeat with
shortened Acyl CoA 3
Enters
CAC
4
The first three rounds in the
degradation of palmitate
Two carbon units are sequentially

removed from the carboxyl end of
the fatty acid.
The reaction for one round of β-oxidation is:
The complete reaction for C16 palmitoyl CoA is:
Processing of the products of the complete reaction by cellular respiration would

generate 106 molecules of ATP (or is it 108 – is the book wrong?).
Degradation of fatty acids with an odd number of carbons
β-Oxidation of fatty acids with odd numbers of carbons

generates propionyl CoA in the last thiolysis reaction.
Propionyl carboxylase, a biotin enzyme, adds a carbon to

propionyl CoA to form methylmalonyl CoA
Succinyl CoA, a citric acid cycle component, is

subsequently formed from methylmalonyl CoA by
methylmalonyl CoA mutase, a vitamin B12 requiring
enzyme.
The conversion of propionyl CoA into succinyl CoA
Propionyl CoA, generated from fatty acids having an odd number of
carbon atoms as well as from some amino acids, is converted into
the citric acid cycle intermediate succinyl CoA.
Ketone bodies—acetoacetate, 3-hydroxybutyrate, and acetone—are synthesized from
acetyl CoA in liver mitochondria and secreted into the blood for use as a fuel by some
tissues such as heart muscle.
3-Hydroxybutyrate is formed upon the reduction of acetoacetate. Acetone is generated by

the spontaneous decarboxylation of acetoacetate.
In tissues using ketone bodies, 3-hydroxybutyrate is oxidized to acetoacetate, which is

ultimately metabolized to two molecules of acetyl CoA.
The formation of ketone bodies
The ketone bodies—acetoacetate, D-3-hydroxybutyrate, and acetone—are formed from
acetyl CoA primarily in the liver. Enzymes catalyzing these reactions are
(1) 3-ketothiolase, (2) hydroxymethylglutaryl CoA synthase,
(3) hydroxymethylglutaryl CoA cleavage enzyme, and (4) D-3-hydroxybutyrate
dehydrogenase. Acetoacetate spontaneously decarboxylates to form acetone.
Ketone bodies are a crucial fuel source during starvation

The utilization of 3-hydroxybutyrate and
acetoacetate as a fuel
3-Hydroxybutyrate is oxidized to
acetoacetate with the formation of NADH.
Acetoacetate is then converted into two
molecules of acetyl CoA, which then enter
the citric acid cycle.
Fats are converted into acetyl CoA, which is then processed by the citric acid cycle.
Oxaloacetate, a citric acid cycle intermediate, is a precursor to glucose.
However, acetyl CoA derived from fats cannot lead to the net synthesis of oxaloacetate or
glucose because although two carbons enter the cycle when acetyl CoA condenses with
oxaloacetate, two carbons are lost as CO2 before oxaloacetate is regenerated.

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Tymoczko • Berg • Stryer

Biochemistry: A Short Course

Three fatty acids

Used as energy storage

Disadvantages of triacylglycerols as energy storage

Two amphipathic bile salts that are cholesterol derivatives

1. Chylomicrons (transport dietary cholesterol to tissues)

Dietary lipids are hydrolyzed by lipases in three

The fatty acids are taken up by cells and used

Glycerol also enters the liver, where it can be

Phosphorylated perilipin activates

Two carbon units are sequentially

The complete reaction for C16 palmitoyl CoA is:

Processing of the products of the complete reaction by cellular respiration would

β-Oxidation of fatty acids with odd numbers of carbons

Propionyl carboxylase, a biotin enzyme, adds a carbon to

Succinyl CoA, a citric acid cycle component, is

3-Hydroxybutyrate is formed upon the reduction of acetoacetate. Acetone is generated by

In tissues using ketone bodies, 3-hydroxybutyrate is oxidized to acetoacetate, which is

Ketone bodies are a crucial fuel source during starvation

Oxaloacetate, a citric acid cycle intermediate, is a precursor to glucose.

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