Friday, September 05, 2008

Into the Textbooks It Goes

This week's issue of Science contains an important paper.
Maier, T,, Leibundgut, M. and B. Nenad (2008) The Crystal Structure of a Mammalian Fatty Acid Synthase. Science 321:1315-1322.
We've known for a long time that this is a very important enzyme and that it's a classic example of a little protein machine combining the activities of may different enzymes in order to carry out the complex reactions of fatty acid synthesis. Here's how I described it in the last edition of my book ...
In bacteria, each reaction in fatty acid synthesis is catalyzed by a discrete monofunctional enzyme. This type of pathway is known as a type II fatty acid synthesis system (FAS II). In animals, the various enzymatic activities are localized to individual domains in a large multifunctional enzyme and the complex is described as a type I fatty acid synthesis system (FAS I). The large animal polypeptide contains the activities of malonyl/acetyl transferase, 3-ketoacyl-ACP synthase, 3-ketoacyl–ACP reductase, 3-hydroxyacyl–ACP dehydratase, enoyl–ACP reductase, and thioesterase. It also contains a phosphopantetheine prosthetic group (ACP) to which the fatty acid chain is attached. Note that the malonyl CoA:ACP transacylase enzyme shown in Figure 16.3 is replaced by a transferase activity in the FAS I complex. This transferase catalyzes a substrate loading reaction where malonyl CoA is covalently attached to the ACP-like domain on the multienzyme polypeptide chain. The eukaryotic enzyme is called fatty acid synthase.
The structure (shown below) will be going right into the textbooks.


  1. No, of course it's not irreducibly complex. It is generally understood that multifunctional enzymes arose in the name of efficiency from individual activities. Another recent paper in Science (on piruvate carboxylase structure, 2007, 317:1076) is an example. Some bugs have individual enzymes, some merged them together. Nature does not care - whatever works.

    That aside, what a great paper. Kudos to authors for perseverance and getting the resolution down.

  2. DK says,

    No, of course it's not irreducibly complex.

    Yes it is irreducibly complex. If you take away any of the component subunits then the complex will not do its job. That's the definition of irreducibly complex.

    The fact that we understand how irreducibly complex structures can evolve is a different matter. It means that the Intelligent Design Creationists are completely wrong about that.

    The bottom line is: irreducibly complex systems exist and we understand perfectly well how they evolved.

  3. Ah, yes, it is irreducibly complex if the definition is this: "A single system which is composed of several interacting parts that contribute to the basic function, and where the removal of any one of the parts causes the system to effectively cease functioning" (taken from Wikipedia). But then just about everything is irreducibly complex and it becomes an argument about semantics of "effectively cease functioning is". I imagine that if you take away ACP from FAS, it will still work - just very inefficiently.