Question

EOS Fatty acid metabolism: Q1 1 point possible (graded) Fatty acid synthase is primed with two molecules at the beginning of odd-chain fatty acid synthesis. What are these TWO molecules? Propionyl-COA Palmitoyl-CoA Malonyl-CoA Acetyl-COA I Acyl-Coa

Answer 1

Answer: Odd chain fatty acids contain odd number of carbon atoms. The most common odd chain fatty acids are pentadecanoic acid (15C) and heptadecanoic acid (17C). The biosynthesis of odd chain fatty acids require propionyl CoA as a primer instead of acetyl CoA which is used in the biosynthesis of even chain fatty acids. The condensation of propionyl CoA and malonyl CoA results in the formation of 3-oxovaleryl ACP, which serves as the starting point of odd chain fatty acid synthesis. So propionyl CoA and malonyl CoA are the two molecules by which fatty acid synthase is primed at the beginning of odd chain fatty acid synthesis.

Answer: The above structure of the fatty acid represents Stearic acid (18C) which is an even chain fatty acid.

A. For the synthesis of 1 molecule Stearic acid (18C), a total of 8 cycles is required. In each cycle, one molecule of malonyl CoA is invested, therefore, to synthesize one molecule of stearic acid, number of molecules of malonyl CoA would be invested is (1$\times$8)=8 molecules.

B. There are two reduction reactions occuring in each cycle of even chain fatty acid synthesis. The first reduction occurs when acetoacetyl ACP is reduced by NADPH dependent beta-keto acyl reductase to form beta-hydroxy fatty acyl ACP. The second reduction occurs when the enoyl ACP is reduced by enoyl reductase utilizing a 2nd molecule of NADPH to form butyryl ACP. So there is an involvement of 2 molecules of NADPH in each cycle. Therefore, for 8 cycles to synthesize one molecule of stearic acid, number of molecules of NADPH would be invested is (2$\times$8)=16 molecules.

C. Two molecule of ATP is utilized in the first step of fatty acid synthesis. The carboxylation of acetyl CoA to form malonyl CoA catalyzed by the enzyme Acetyl CoA carboxylase, requires the investment of two ATP molecules, as it is converted to AMP. So for the synthesis of one molecule of stearic acid, 2 molecules of ATP would be invested.

Answer: The starting material for the synthesis of fatty acid is acetyl CoA. It is formed inside the mitochondria from pyruvate. The inner membrane is not freely permeable to acetyl CoA. Hence acetyl CoA units are delivered to the cytoplasm as citrate via citrate/oxaloacetate shuttle. Citrate is transported from mitochondria by a tricarboxylic acid transporter. In the cytoplasm, citrate is cleaved to oxaloacetate and acetyl CoA in the cytoplasm. The enzyme is ATP citrate lyase. The oxaloacetate can return to the mitochondria as malate or pyruvate. For every molecule of acetyl CoA delivered to the cytoplasm, one molecule of NADPH is formed and reducing equivalents are generated in the cytoplasm. So the two primary functions of the citrate/oxaloacetate shuttle is: to generate acetyl CoA in the cytoplasm and to generate NADPH for FAS.