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Chapter 19: Lipids: Fatty Acid Synthesis

In studies with a particular cell line in culture you discover that the rate of mitochondrial fatty acid oxidation increases when the cells are stimulated to increase their rate of de novo fatty acid synthesis. This observation is quite unexpected since these 2 processes do not normally coincide. Which of the following enzymes involved in fatty acid synthesis is most likely to be altered thus, allowing for fat oxidation to be enhanced along with an increase in fat synthesis?

A. acetyl-CoA carboxylase 2

B. ATP-citrate lyase

C. fatty acid synthase

D. malic enzyme

E. steroyl-CoA desaturase

Answer A: During fatty acid synthesis the malonyl-CoA produced from acetyl-CoA carboxylase 2 (ACC2) directly interacts with carnitine palmitoyltransferase I (CPT I) at the outer mitochondrial membrane to prevent fatty acyl-CoA movement into the mitochondria. A defect in ACC2 activity would therefore lead to reduced inhibition of regulated mitochondrial transport of fatty acyl-CoA resulting in increased fat oxidation from the newly synthesized fatty acids.

You are studying fatty acid synthesis in a cell line isolated from a hepatic cancer. You discover that addition of glucose-6-phosphate does not lead to an increase in the rate of palmitic acid synthesis as is the situation in normal hepatic cells. Which of the following proteins is most likely to be altered in the hepatic cancer cells leading to the obtained results?

A. acetyl-CoA carboxylase

B. ATP-citrate lyase

C. ChREBP

D. fatty acid synthase

E. steroyl-CoA desaturase

Answer D: Regulation of de novo fatty acid synthesis takes place primarily at the level of acetyl-CoA carboxylase (ACC) but also at the level of fatty acid synthase (FAS). FAS is regulated by both short-term and long-term mechanisms. Short-term regulation is primarily the result of the allosteric activation of FAS by phosphorylated sugars, such as glucose 6-phosphate.

Gas chromatographic analysis of fatty acids present in cells isolated from a particular strain of mice shows little to no palmitoleic and oleic acid but expected levels of palmitic acid. A defect in which of the following proteins is most likely causing the absence of the 2 fatty acids?

A. acetyl-CoA carboxylase

B. ATP-citrate lyase

C. ChREBP

D. fatty acid synthase

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