Fatty acid synthesis versus fatty acid oxidation

“Although chemical processes involved are the same, Fatty acid synthesis is not simply a reversal of fatty acid oxidation.”             

Fatty acid synthesis seems simply a reversal of the degradative pathway, but it consists of a new set of reactions, exemplifying the principle that synthetic and degradative pathways are almost always distinct. Some important differences between the pathways are:

1. Synthesis takes place in the cytosol, in contrast with degradation, which takes place primarily in the mitochondrial matrix.
2. Intermediates in fatty acid synthesis are covalently linked to the sulfhydryl groups of an acyl carrier protein (ACP), whereas intermediates in the fatty acid breakdown are covalently attached to the sulfhydryl group of coenzyme A.
3. The enzymes of fatty acid synthesis in higher organisms are joined in a single polypeptide chain called fatty acid synthase. In contrast, degradative enzymes do not seem to be associated.
4. The growing fatty acid chain is elongated by the sequential addition of two-carbon units derived from acetyl CoA. The activated donor of two-carbon units in the elongation step is malonyl ACP. The release of CO2 drives the elongation reaction.
5. The reductant in fatty acid synthesis is NADPH, whereas the oxidants in fatty acid degradation are NAD⁺and FAD.
6. Elongation by the fatty acid synthase complex stops on the formation of Palmitate(C16). Further elongation and the insertion of double bonds are carried out by other enzyme systems.

Overview of fatty acid oxidation- The process of degradation converts an aliphatic compound into a set of activated acetyl units (acetyl CoA) that can be processed by the citric acid cycle. An activated fatty acid is oxidized to introduce a double bond; the double bond is hydrated to introduce oxygen; the alcohol is oxidized to a ketone; and, finally, the four-carbon fragment is cleaved by coenzyme A to yield acetyl CoA and a fatty acid chain two carbons shorter. If the fatty acid has an even number of carbon atoms and is saturated, the process is repeated until the fatty acid is completely converted into acetyl CoA units. (Figure)

Overview of fatty acid synthesis- Fatty acid synthesis is essentially the reverse of this process. Because the result is a polymer, the process starts with monomers in this case with an activated acyl group (most simply, an acetyl unit) and malonyl units (see Figure). The malonyl unit is condensed with the acetyl unit to form a four-carbon fragment. To produce the required hydrocarbon chain, the carbonyl must be reduced. The fragment is reduced, dehydrated, and reduced again, exactly the opposite of degradation, to bring the carbonyl group to the level of a methylene group with the formation of butyryl CoA. Another activated malonyl group condenses with the butyryl unit and the process is repeated until a C16 fatty acid is synthesized. (See figure)

 

 

Figure-Showing the chemical processes involved in fatty acid synthesis and oxidation