FASynthesis - Topics for Fatty Acid Biosynthesis Regulation...

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Regulation of Fatty Acid Biosynthesis Dr. Susan C. Frost BCH 6206 Chapter 25 pgs 930-942 copyright: Susan C. Frost Topics for Fatty Acid Biosynthesis Substrate for Fatty Acid Biosynthesis Acetyl CoA Carboxylase I and 2 Allosteric regulation Covalent modification Polymerization Hormone action Fatty Acid Synthase Multifunctional catalysis Transcriptional regulation Overview of Pathways for FA and TG synthesis ! ! $ $ $ $ ! $ $ ! Provision of Acetyl CoA via Citrate Figure 1 Glucose Glucose 6-phosphate Fructose 6-phosphate Glyceraldehyde 3-P Pyruvate Pyruvate Acetyl CoA Citrate Oxaloacetate Citrate Acetyl CoA OAA Malonyl CoA Palmitate -Ketoglutarate Malate Malate NAD NADH + H + HEX - P NADP NADPH + H + CO 2 Acetyl CoA Carboxylase 1 Fatty Acid Synthase mitochondria cytosol Malonyl CoA Acetyl CoA Carboxylase 2 Acetyl CoA Carboxylase Figure 2 CH 3 -C ~ S-CoA O HOOC-CH 2 -C ~ S-CoA O ATP + CO 2 ADP + Pi biotin Rate limiting step Allosteric regulation (citrate and fatty acyl CoA's) Polymerization (citrate, fatty acyl CoA, insulin) Covalent Modification (phosphorylation) Two different forms: ACC1 and ACC2 ACC1 is highly expressed in liver and adipose and is localized to the cytosol ACC2 is expressed in heart and skeletal muscle, and to a lesser extent in liver and is localized to the mitochondria Malonyl CoA from either enzyme serves as a key metabolic regulator Question: Are there two different pools of malonyl CoA?
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Effect of Insulin and Citrate on Polymerization of ACC Figure 3 0 0.25 0.50 0.75 10 20 A 280 10 20 20 40 60 Acetyl CoA Carboxylase Activity (% of total) 10 20 0 0.25 0.50 0.75 10 20 20 40 60 + insulin + citrate + citrate + insulin control Adipose tissue was treated or not with insulin, extracts prepared and treated or not with citrate. Partially purified ACC (equivalent to 500mg of original tissue) was
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This note was uploaded on 06/07/2011 for the course BCH 6206 taught by Professor Staff during the Spring '08 term at University of Florida.

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FASynthesis - Topics for Fatty Acid Biosynthesis Regulation...

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