Protein of the Month |
June 2007
MORE ON THIS MONTH�S PROTEIN
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OTHER PROTEINS OF INTEREST |
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Molecule of the Month: Fatty Acid Synthase |
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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.�
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