Download Biochemistry: A Short Course

Tymoczko • Berg • Stryer
Biochemistry: A Short Course
Second Edition
CHAPTER 27
Fatty Acid Degradation
Dietary Lipid (Triacylglycerol) Metabolism
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In the small intestine, fat particles are coated with bile salts
and digested by pancreatic lipases
Two amphipathic bile salts that are cholesterol derivatives
Figure 27.1 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 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.
Figure 27.5 Beta Oxidation of Fatty Acids
1
2
Repeat with
shortened Acyl CoA
3
Enters
CAC
4
Figure 27.6 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.
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.
Figure 27.9
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.
Figure 27.10 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
Figure 27.11
The utilization of D-3-hydroxybutyrate and
acetoacetate as a fuel.
D-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.