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

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