Fatty Acid Biosynthesis：脂肪酸的生物合成.pptVIP

Chapter 25: Fatty Acid Biosynthesis CH234 Bruce A. Hathaway * Acetyl Coenzyme A Acetyl Coenzyme A is the starting material for fatty acid biosynthesis. It is derived from metabolism of carbohydrates, fats and some amino acids. The two-carbon piece provides the carbons for the new fatty acid. Acetyl Coenzyme A * * Acetyl Coenzyme A (AcCoA) Overview of Metabolism And Energy Production * Step 1: Preparation of Malonyl CoA Acetyl CoA reacts with bicarbonate to form Malonyl CoA. This is energy-requiring, so hydrolysis of an ATP is used to drive the reaction. Malonyl CoA is more reactive than Acetyl CoA. * Step 2: Transthioesterifaction Both Acetyl CoA and Malonyl CoA are connected to Acetyl Carrier Protein (ACP), which is another thiol. One thiol replaces another to make a different thioester. ACP shuttles the molecules to the different enzymes needed to do the following reactions. * Step 3: C-C Bond Formation Malonyl ACP loses CO2 to make a carbon anion. An acetyl ACP reacts with the carbon anion to give a four-carbon β-ketoester. * Step 4: Reduction of the Ketone The ketone is reduced to an alcohol. Only one stereoisomer is produced: why? NADPH functions similar to NaBH4 in this reaction. * NADPH NADPH is similar to NADH. It has an extra phosphate, while NADH has an H. Metabolism uses NADH. Biosynthesis uses NADPH. * Reduction of the Ketone with NADPH NADPH donates a hydride H- to reduce the ketone: the H+ comes from water, ultimately. Only one enantiomer is formed. * Step 5: Dehydration of the Alcohol The alcohol is specifically dehydrated to the trans alkene. Again, only one isomer is formed. * Step 6: Reduction of the Alkene NADPH + H+ reduces the C=C to an alkane. We have now made a four-carbon “fatty acid”. * Elongation of Fatty Acids The Butyroyl-ACP replaces the Acetyl-ACP in Step 3, to make a 6-carbon ketoacid. * Elongation of Fatty Acids The 6-carbon keto-acid is reduced, dehydrated, and reduced again (steps 4-6), to make the six-carbon fatty acid. This can