Lecture30-2009-Li - 1 Fatty Acid Biosynthesis Lecture 30...

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1 Fatty Acid Biosynthesis Lecture 30 Chapter 20-4 and 5 Office hours: 1:00 to 2:00 pm Monday, Wednesday & Friday CMM Room 142 Phone: 632-1401 [email protected]
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2 Pyruvate Acetyl-CoA Fatty acids CO 2 Pyruvate dehydrogenase complex Glucose Glycogen Liver stores excess glucose as glycogen or fatty acids: Glycolysis Fatty acid synthesis Lecture-35, 36
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3 Fatty acid biosynthesis shares chemical similarities to ß-oxidation, but it occurs in the cytoplasm Figure 20-23
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4 Acetyl-CoA is generated in the mitochondrial matrix (pyr deH in matrix), but no transporter for Acetyl-CoA in inner membrane. Use citrate as carrier molecule. Uses ATP to drive synthesis of thioester Provides cytoplasmic NADPH Figure 20-24 Acetyl-CoA in MT is transported into cytosol as citrate
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5 Acetyl-CoA is “activated” by adding a CO 2 , generating Malonyl-CoA, the donor for fatty acid synthesis. Acetyl-CoA carboxylase (biotin) (ACC): Acetyl-CoA + HCO 3 - + ATP --> Malonyl-CoA + ADP + Pi Two step reaction, similar to pyruvate carboxylase and proprionyl-CoA carboxylase. Page 703
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6 Mammalian Fatty Acid Synthase (FAS): 534 kDal protein with 6 enzymatic activities (bacteria have 7 independent proteins). Figure 20-27a 1. MAT – malonyl/acetyl CoA ACP transferase 2. KS – keto synthase 3 . ER – Enoyl reductase 4. KR – keto reductase 1. DH – hydroxylacyl dehydrogenase 2. TE – palmitol thioesterase 6 enzymatic activities 7 cycles of C 2 elongation Palmitate
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7 ß-oxidation occurs with fatty acid linked to CoA , but biosynthesis occurs linked to Acyl-Carrier Protein (ACP) Figure 20-23
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8 ACP is part of FAS (534 kDa): Figure 20-27a Bacterial ACP 10 kDa
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