Subcellular location of fatty acid synthesis in eukaryotes Where does de novo fatty acid synthesis (lipogenesis) primarily occur inside non-plant eukaryotic cells?

Introduction / Context:
Fatty acid synthesis and fatty acid oxidation are spatially segregated in eukaryotic cells to enable reciprocal regulation. Identifying the correct compartment for de novo synthesis helps explain how metabolic pathways are coordinated and how malonyl CoA regulates mitochondrial fatty acid entry.

Given Data / Assumptions:

• Non plant eukaryotes (e.g., animals) synthesize fatty acids predominantly in the cytosol.
• Key enzymes include acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS).
• Plants additionally carry out synthesis in chloroplast stroma.

Concept / Approach:

Acetyl CoA generated in mitochondria is exported as citrate, which ATP citrate lyase converts back to cytosolic acetyl CoA. ACC produces malonyl CoA, and the multidomain FAS elongates the chain, using NADPH from the pentose phosphate pathway and malic enzyme. Malonyl CoA simultaneously inhibits carnitine palmitoyltransferase 1, preventing futile cycling with mitochondrial β oxidation.

Step-by-Step Solution:

Verification / Alternative check:

Subcellular fractionation and immunolocalization place ACC and FAS in cytosol; pharmacologic inhibitors (e.g., TOFA) act on cytosolic enzymes, altering lipogenesis.

Why Other Options Are Wrong:

Mitochondrial matrix is the site of β oxidation, not synthesis. The plasma membrane and nucleus are not primary lipogenesis sites. ER participates in elongation/desaturation of products but is not the primary site of de novo synthesis initiation.

Common Pitfalls:

Assuming synthesis occurs where oxidation occurs or overlooking the role of citrate shuttle and cytosolic NADPH.

Final Answer:

Cytosol (with enzymes such as ACC and fatty acid synthase)