Protein of the Month

June 2007






Molecule of the Month: Fatty Acid Synthase




ExPASy Protein Spotlight


Fatty Acid Synthase

By Jennifer McDowall


Fatty acids are essential nutrients for all organisms, except archaea.  A fatty acid is a carboxylic acid with a long, unbranched aliphatic tail that is either saturated or unsaturated. Within cells, fatty acids serve many vital functions:

·        As major components of cell membranes, including internal organelle membranes (each phospholipid contains two fatty acid tails)

·        For  energy storage - (yields significantly more energy than carbohydrates, for the same mass)

·        As messenger substances (e.g. ceramide is a fatty acid-containing messenger in cytokine-induced apoptosis)

·        For the post-translational modification of certain proteins

The synthesis of fatty acids is essentially the reverse chemistry of its degradation by oxidation, both pathways involving an activated two-carbon intermediate, acetyl-CoA.  Therefore, a cell needs a means of separating the two opposing pathways in order to allow their independent control.  In eukaryotes, this is achieved both physically and chemically:

·        Fatty acid synthesis occurs in the cytoplasm, while its oxidation occurs in mitochondria

·        Fatty acid synthesis requires the oxidation of the co-factor NADPH, while fatty acid oxidation requires the reduction of FAD+ and NAD+

In addition, distinct enzymes control the two pathways, permitting a further level of control.  Fatty acid synthesis is carried out by fatty acid synthase.

Fatty Acid Synthase, Lipid Factories


            A battery of enzymes are required to synthesise fatty acids, however their organisation differs among species.  Fatty acid synthetase (FAS) can be divided into two groups based on the organisation of their catalytic units:


Type I FAS systems


Type I FAS systems are multi-enzyme complexes that contain all the catalytic units as distinct domains covalently linked into one (alpha) or two (alpha and beta) polypeptides.  Type I systems include eukaryotic, as well as a few bacterial, FAS enzymes.  These systems can be further divided into subgroups according to the organisation of individual polypeptides and the domains within these polypeptides:

·        Animal FAS enzymes consist of (alpha)2 homodimers

·        Fungal FAS enzymes consist of (alpha)6(beta)6 dodecamers

·        A few bacterial FAS enzymes consist of (alpha)6 hexamers

            Type I FAS systems carry out multiple steps of fatty acid synthesis in each sterically isolated reaction chamber.  Mammalian FAS is thought to have evolved through gene fusion.


Type II FAS systems 


In type II FAS systems, the enzymes exist as distinct, individual proteins, where each protein catalyses a single step in the reaction pathway.  Most prokaryotic FAS systems fall into this category, as well as certain plant FAS systems. 



Next:  How Fatty Acids are Made