Why does fatty acid synthesis require reducing power

Why does fatty acid synthesis require reducing power? What are sources of NADPH?

The correct answer and explanation is:

Fatty acid synthesis requires reducing power primarily to reduce the carbon-carbon bonds during the elongation process. In the synthesis of fatty acids, acetyl-CoA molecules are added sequentially to form long chains, and each addition involves the reduction of a carbonyl group to a methylene group (–CH2–). This reduction is facilitated by NADPH, a molecule that donates electrons in the form of hydrogen ions (H+) and electrons (e–), thereby reducing the intermediates in the fatty acid chain.

The process of fatty acid synthesis occurs in the cytoplasm, and it is catalyzed by the fatty acid synthase complex. For each cycle of fatty acid elongation, two NADPH molecules are required: one for the reduction of the β-keto group to an alcohol and another for the reduction of the enoyl group to a saturated bond. The NADPH serves as the reducing agent in these reactions.

Sources of NADPH include several metabolic pathways:

  1. Pentose Phosphate Pathway (PPP): This is the primary source of NADPH in cells. The oxidative phase of the PPP generates NADPH while converting glucose-6-phosphate into ribulose-5-phosphate. The reduction of NADP+ to NADPH occurs during the conversion of 6-phosphogluconate to ribulose-5-phosphate.
  2. Malic Enzyme: This enzyme converts malate to pyruvate, producing NADPH in the process. It is particularly important in tissues like the liver and adipose tissue, where fatty acid synthesis is prominent.
  3. Isocitrate Dehydrogenase: In some tissues, the NADPH can also be generated by the action of isocitrate dehydrogenase in the citric acid cycle, especially when isocitrate is converted to α-ketoglutarate, reducing NADP+ to NADPH.

Together, these pathways ensure that the cell has a sufficient supply of NADPH to drive the anabolic processes like fatty acid synthesis, which are energy-intensive and require ongoing reductions for the elongation of fatty acid chains.

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