24 Fatty Acid Synthesis

24 Fatty Acid Synthesis - B iochemis ry E duca ion...

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Unformatted text preview: B iochemis ry E duca ion Department of iochemistry & Molecular iology University of New Mexico BIOC 423 Int oducto y Biochemist y 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 leaves the mitochondrion. • Understand how fatty acids can be elongated and unsaturated. • Know how fatty acids are incorporated into storage fat. OUTLINE Transport of "acetyl S-CoA" into the cytoplasm When to use the different carbon shuttles Malic enzyme an alternate source of NADPH Reactions of fatty acid synthesis Fatty acid synthase complex Activation Comparing synthesis with oxidation Why Thiolase will not work as the first step in fatty acid synthesis Regulation of fatty acid synthesis Acetyl-SCoA carboxylase Inhibition of fatty acid oxidation Elongation and unsaturation Essential fatty acids LECTURE Fat is an excellent storage form of energy that we have already discussed on several occasions. We synthesize fatty acids, as a method to store potential energy, when the diet contains excess calories. Excess fatty acids from the diet also can be incorporated directly into triacylglycerols (TAGs) in adipose tissues and excess carbohydrates and carbon skeletons from amino acid degradation can all be stored in adipose as TAGs. Unlike oxidation, the biosynthesis of fatty acids occurs in the cytosol of the liver. The newly synthesized fatty acids are then converted into TAGs and synthesized into lipoproteins for transport to the adipose tissue. Insulin is the hormone that turns on the reactions of fatty acid synthesis. Fatty acid synthesis takes place in the cytoplasm The synthesis of fatty acid happens in the cytoplasm and requires acetyl-SCoA and NADPH. However, the carbon starting materials for synthesis are in the matrix of the mitochondria. Glucose from the diet was converted to acetyl-SCoA, and amino acid oxidation takes place in the matrix. Since the mitochondrial matrix is impermeable to acetyl-SCoA, before we can synthesize fatty acid we must first transport acetyl-SCoA into the cytoplasm. The transport of acetyl-SCoA from the matrix to the cytoplasm requires the conversion of acetyl-SCoA into citrate. We already studied the citrate synthase enzyme during our discussions of the CAC. Review: from glycolysis pyruvate is converted into acetyl-SCoA by pyruvate dehydrogenase and into oxaloacetate by pyruvate carboxylase. In the mitochondrial matrix the citric acid cycle enzyme citrate synthase condenses oxaloacetate and acetyl-SCoA into citrate. The energy driving this reaction is the hydrolysis of the thiol ester of acetyl-SCoA....
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24 Fatty Acid Synthesis - B iochemis ry E duca ion...

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