10-14-11 Fatty acid oxidation

1. 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

2. 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

3. 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

4. Depending on the animal’s current metabolic needs, fatty acids may be: Converted to triacylglycerols Degraded to generate energy Used for membrane synthesis

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

6. Triacylglycerol Synthesis

7. 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

9. Fatty acids are linked to Coenzyme A before oxidation • An acyl-adenylate intermediate is formed acyl CoA synthetase

10. 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

11. Fatty Acid Transport into the Mitochondrion

12. 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

13. 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 L-3-hydroxyacyl CoA dehydrogenase ketothiolase

15. 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)

16. Ketone Body Formation * D-3-hydroxybutyrate dehydrogenase 3-ketothiolase HMG CoA cleavage enzyme hydroxymethylglutaryl CoA synthase * mitochondrial matrix Ketone Bodies - excess acetyl-CoA is converted to ketone bodies (ketogenesis) Forms acetoacetate, b-hydroxybutyrate and acetone