Ch21.1 - Chapter 21 - Lipid Biosynthesis •Fatty acid...

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Unformatted text preview: Chapter 21 - Lipid Biosynthesis •Fatty acid synthesis and regulation •Triacylglycerol synthesis β-Oxidation and Fatty Acid Synthesis Why is malonyl-CoA used in fatty acid synthesis? Ultimately, all carbons in fatty acids are derived from acetyl-CoA. Condensing two molecules of acetyl-CoA would be difFcult -- no good leaving group So cell “activates” acetyl-CoA for making fatty acid chains Enzyme responsible -- acetyl-CoA carboxylase (forms malonyl-CoA) Acetyl-CoA Carboxylase (ACC) : activation of acetyl-CoA Acetyl-CoA + ATP + HCO 3 Malonyl-CoA + ADP + P i (Biotin is temporary carrier of carboxylate group) Figure 21-1 Mechanism is similar to that of pyruvate carboxylase Mechanism is similar to that of pyruvate carboxylase The general scheme for making fatty acids: There are two acyl group carriers in fatty acid synthase: 1) a Cys -SH group 2) phosphopantetheine -SH group Acyl Carrier Protein (ACP) Figure 21-5 Recall, thioester cleavage is very exergonic… ACP- acyl carrier Protein (-SH) KS- β-ketoacyl- ACP synthase (-SH) Fatty Acid Synthase Seven different enzyme activities! Mammalian FA synthase Malonyl/Acetyl-CoA-ACP transferase (MAT) activity catalyzes the transfer of acetyl group from acetyl-CoA to a Cys sulfhydryl group of β-ketoacyl- ACP synthase (KS) domain Fatty acid synthesis frst “initiation” step Second “initiation” step : Malonyl group is esterifed to -SH oF ACP by Malonyl/acetyl-CoA-ACP transFerase (MAT) Thioester intermediates formed by fatty acid synthase: 1)¡ormation primes acyl groups For nucleophilic attack 2)Long pantetheine arm on ACP allows substrate to visit multiple active sites while covalently attached to enzyme 3)Keeps increasingly hydrophobic substrate on soluble enzyme Cycle Step 1 -- Condensation (catalyzed by KS domain) Cycle Step 2 -- Reduction (KR)...
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This note was uploaded on 09/21/2010 for the course CH 53380 taught by Professor Raymond during the Spring '10 term at University of Texas.

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Ch21.1 - Chapter 21 - Lipid Biosynthesis •Fatty acid...

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