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Lecture 10

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McGill University
Biology (Sci)
BIOL 201
Greg Brown

Lecture 10 Fatty Acid Biosynthesis Humans take in enough fatty acids to sustain metabolism, most people have no need for synthesizing more fatty acids. Carboxylation of acetyl CoA to form malonyl CoA, catalyzed by acetyl CoA carboxylase. Acetyl CoA + HCO3- + ATP -> Malonyl CoA + ADP + Pi, endergonic, coupled to ATP hydrolysis, more or less irreversible. Regulated by the phosphorylation of the enzyme, done by the AMP-dependent protein kinase, which is switched off when AMP levels are high. Acyl groups of the malonyl CoA and acetyl CoA are transferred to an Acyl Carrier Protein, which has a covalently attached phosphopantetheine group, which has a sulfhydro group attached to the groups via a thioester bond. Acetyl ACP and Malonyl ACP (2C and 3C) react to form acetoacetyl ACP (4C) an CO2. Energy released by the CO2 release is consumed by the formation of the acetoacetyl ACP. AACP is then dehydrated, reduced again, and eventually form butyryl ACP. Butyryl ACP will react with malonyl ACP to form a 6C aliphatic fatty acyl ACP. In plants, all of the proteins are separate, but in mammals, ACP and enzymes catalyzing all these steps are components of a single fused polypeptide. The reduction reaction requires NADP+, not NADPH. Fatty acid biosynthesis occurs in the cytosol while the acetyl CoA is produced in the mitochondria, however, acetyl CoA cannot cross the inner mitochondrial membrane due to a lack of transfer proteins. When rate of the Kreb’s Cycle drops, citrate accumulation in the mitochondria lead to citrate being transferred into the cytosol. Citrate is the allosteric inhibitor of phosphofructose kinase, and forces itself out. Citrate cleavage enzyme that exists in the cytosol breaks citrate down to form acetyl CoA and oxaloacetate. OAA is then formed into malate by the reduction of NADP into NADPH, which also forms pyruvate, th
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