10-14-11 Fatty acid oxidation
Acetyl-CoA, the energy-rich molecules composed of
coenzyme A and the two carbon acetyl group,
plays a preeminent role in the metabolism of
lipids
Precursor in fatty acid biosynthesis and isoprenoid
biosynthesis
Fatty acids are an important and efficient energy
source for many cells
After triacylglycerol molecules
are ingested, they are
mixed with bile salts and
digested by pancreatic
lipases into fatty acids
and monoacylglycerol
Both are transported into the
cell from the intestinal
lumen
Eventually reconverted to
triacylglycerol, converted
to chylomicrons and
secreted into the lymph
Digestion and Absorption of Triacylglycerols in the Small Intestine
Most of the triacylglycerol content in circulating
chylomicrons is removed by skeletal muscle
and adipose tissue cells (adipocytes)
Lipoprotein lipase breaks down these triacylglycerol
molecules into fatty acids and glycerol
Fatty acids are taken up by the cells and glycerol is
transported to the liver
When lipoprotein lipase has removed 90% of the
triacylglycerols in chylomicrons, the
chylomicron remnants are removed from the
blood by the liver
Depending on the animal’s current metabolic needs,
fatty acids may be:
Converted to triacylglycerols
Degraded to generate energy
Used for membrane synthesis
8P2-4
In triacylglycerol (TAG) synthesis (lipogenesis),
glycerol-3-phosphate or dihydroxyacetone
phosphate reacts sequentially with three
molecules of acyl-CoA
Acyl-CoA molecules are fatty acid esters of CoASH
8P2-5
Triacylglycerol
Synthesis
Lipolysis in
adipocytes triggered
by glucagon or
epinephrine
When energy reserves are low, the body’s fat stores
are mobilized in a process termed lipolysis
Lipolysis occurs during fasting, during vigorous
exercise and in response to stress
Fatty acid binding proteins are responsible for
transporting the fatty acids into target
organelles
8P2-8
Fatty acids are linked to Coenzyme A before oxidation
acyl CoA
synthetase
An acyl-adenylate intermediate is formed
8P2-9
Carnitine is used to transfer acyl groups into the
mitochondrion where most b-oxidation occurs
1. Acyl-CoA converted into acylcarnitine
2. Translocase transfers
acylcarnitine into matrix
3. Acyl-CoA regenerated
4. Carnitine recycled to
intermembrane space
8P2-10
Fatty Acid Transport into the Mitochondrion
Fatty Acid Degradation
Most fatty acids are degraded by the sequential
removal of two carbon fragments from the
carboxyl end as acetyl-CoA; this is known as
b-oxidation
Once formed, acetyl-CoA and other short chain
products are used for energy production or as
metabolic intermediates
The b-oxidation of saturated fatty acids is a series of
four reactions that constitute one cycle of
b-oxidation
During each later cycle, a two carbon fragment is
removed (b-oxidation spiral)
Acetyl-CoA molecules produced are used in the
citric acid cycle (or for isoprenoid synthesis)
acyl CoA
dehydrogenase
enoyl CoA
hydratase
ketothiolase
L-3-hydroxyacyl
CoA
dehydrogenase
8P2-14
The Complete Oxidation of a Fatty Acid
The aerobic oxidation of a fatty acid generates a
large number of ATP molecules
The yield of ATP from the oxidation of palmitoylCoA is 108 ATP (106 net)
Ketone Body Formation
* D-3-hydroxybutyrate
dehydrogenase
3-ketothiolase
hydroxymethylglutaryl
CoA synthase
HMG CoA
cleavage
enzyme
* mitochondrial matrix
Ketone Bodies - excess acetyl-CoA is converted to
ketone bodies (ketogenesis)
Forms acetoacetate, b-hydroxybutyrate and acetone
8P2-17
8P2-18