10.4 Fatty acid synthesis
10.4.1 Reactions in fatty acid synthesis
10.4.2 Transport of acetyl-CoA from the mitochondrion to the cytosol
10.4.3 Supply of NADPH for fatty acid synthesis
10.4.4 Cerulenin, a natural inhibitor of fatty acid synthase
Fatty acids can be synthesized from acetyl-CoA. This is the major way of utilizing excess dietary carbohydrates. Fatty acid synthesis occurs mainly in the fat tissue and the liver. Synthesis and degradation of fatty acids are similar in that they involve a cycle of reactions that changes the length of the substrate by two carbon atoms at a time. However, they differ from each other in several aspects:
- Synthesis runs in the cytosol, whereas β-oxidation occurs in the mitochondria. This makes it easier to control the two pathways separately.
- Synthesis uses NADPH rather than NADH and FADH2 to reduce the C=C and C=O double bonds. Use of NADPH drives both reactions toward reduction.
- The C2 subunits that are sequentially added are derived from malonyl-CoA rather than from acetyl-CoA directly. Again, this thermodynamically favours synthesis over degradation.
Factors 2 and 3 both combine to make fatty acid synthesis irreversible. In contrast, β-oxidation is reversible, and reversed β-oxidation is actually used by mitochondria to synthesize their own fatty acids.
The bulk of the work in fatty acid synthesis is accomplished by fatty acid synthase, which is quite an amazing molecule: It combines 8 enzymatic activities on a single polypeptide chain. Its product is palmitic acid (hexadecanoic acid; C16, fully saturated). As stated before, fatty acids vary in their chain lengths and degree of bond saturation. Chain elongation and desaturation is accomplished by additional enzymes, called elongases and desaturases. We just note these here but will not consider them in detail.