10-14-11 fatty acid oxidation
DESCRIPTION
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 - PowerPoint PPT PresentationTRANSCRIPT
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
10-14-11 Fatty acid oxidation
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
8P2-4
Depending on the animal’s current metabolic needs, fatty acids may be:
Converted to triacylglycerols
Degraded to generate energy
Used for membrane synthesis
8P2-5
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
Triacylglycerol
Synthesis
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
Lipolysis in adipocytes triggered
by glucagon or epinephrine
8P2-8
8P2-9
Fatty acids are linked to Coenzyme A before oxidation
An acyl-adenylate intermediate is formed
acyl CoA
synthetase
8P2-10
Carnitine is used to transfer acyl groups into the mitochondrion where most -oxidation occurs
1. Acyl-CoA converted into acylcarnitine
2. Translocase transfers
acylcarnitine into matrix
3. Acyl-CoA regenerated
4. Carnitine recycled to
intermembrane space
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 -oxidation
Once formed, acetyl-CoA and other short chain products are used for energy production or as metabolic intermediates
The -oxidation of saturated fatty acids is a series of four reactions that constitute one cycle of
-oxidation
During each later cycle, a two carbon fragment is removed (-oxidation spiral)
Acetyl-CoA molecules produced are used in the citric acid cycle (or for isoprenoid synthesis)
acyl CoA
dehydrogenase
enoyl CoA
hydratase L-3-hydroxyacyl
CoA
dehydrogenase
ketothiolase
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 palmitoyl-CoA is 108 ATP (106 net)
Ketone Bodies - excess acetyl-CoA is converted to ketone bodies (ketogenesis)
Forms acetoacetate, -hydroxybutyrate and acetone
Ketone Body Formation
3-ketothiolasehydroxymethylglutaryl
CoA synthase
HMG CoA
cleavage
enzyme
* D-3-hydroxybutyrate
dehydrogenase
* mitochondrial matrix
8P2-17
8P2-18