4-423-08FASynthStudent

4-423-08FASynthStudent - Fatty Acid Synthesis Objectives...

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Fatty Acid Synthesis Objectives Understand the role of fatty acid synthesis in intermediary metabolism. Know the subcellular location of fatty acid synthesis. Be able to compare the reactions of fatty acid synthesis and fatty acid oxidation. Understand the regulation of fatty acid synthesis. Know how acetyl-CoA equivalents leave the mitochondrion. Understand that fatty acids can be elongated and unsaturated. Know how fatty acids are incorporated into storage fat. Outline I. Fat is an excellent storage form of energy -Excess fatty acids from diet can be incorporated into triacylglycerols (TAGs) in adipocytes -Excess carbohydrates (and excess carbon skeletons from amino acid degradation) can also be stored in adipocytes as TAGs, but first must be synthesized into fatty acids (FAs) II. Biosynthesis of fatty acids A. Acetyl-CoA is the starting point for FA synthesis - Breakdown of glucose to acetyl-Coa through glycolysis and pyruvate dehydrogenase reaction -FA synthesis occurs in cytosol; acetyl-CoA made in matrix B. Transport of acetyl-CoA to cytosol from matrix: Citrate transporter In matrix, 1. acetyl-CoA produced from glycolysis plus pyruvate dehydrogenase reaction, and from aa degradation 2. Acetyl-CoA + OAA -> citrate + CoA Citrate synthase 3. Citrate out of matrix, into cytosol, through citrate transporter In cytosol: 4. Citrate + CoA + ATP -> OAA + acetyl-CoA + ADP + Pi Citrate lyase Acetyl-CoA now in cytoplasm, can be used for FA synthesis OAA-> Malate
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Malate can return to matrix via MA transporter OR 5. Malate + NADP+ -> pyruvate + CO 2 + NADPH Malic enzyme in cytosol (another way besides PPP to make NADPH). This NADPH can be used for FA biosynthesis! Pyruvate back to matrix via its transporter C. Formation of malonyl-CoA -FAs are synthesized in 2-C pieces, but the pieces added (after the first one) are 3-C pieces, malonyl-CoA -Acetyl-CoA + CO 2 + ATP -> malonyl-CoA + ADP + Pi Acetyl-CoA carboxylase (this enzyme is a 3-part complex); this is a carboxylation reaction, needs ATP, bicarbonate, biotin D. Fatty acid synthesis. Enzyme = fatty acid synthase complex There are four steps in each addition of a 2-carbon piece. But first…an acetyl group and a malonyl group are attached to thiol groups on the fatty acid synthase. This is the “charging” reaction and not considered part of the numbered 4- step sequence that follows: 1. Condensation: -acetyl group (2C) + malonyl group (3C) -> CO 2 + 4-C construct (acetoacetyl-ACP) Note that the CO 2 added to make the malonyl CoA by acetyl CoA carboxylase leaves at this point 2. Reduction using NADPH 3. Dehydration, creates a double bond 4. Reduction using NADPH These four steps are repeated until a 16C saturated FA (palmitate) is made, and released.
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