Stereospecificity of Aconitase

The isomerization of citrate to isocitrate, catalyzed by the enzyme aconitase, is stereospecific. Four stereoisomeric forms of isocitrate are possible from the isomerization of the symmetric citrate precursor, but the reaction catalyzed by aconitase produces only one of the four isomers. The enzyme has an asymmetric binding site for citrate (Figure 14.13). The asymmetric binding site allows the substrate to bind to the enzyme in only one orientation and the subsequent transfer of the hydroxyl group occurs only according to this orientation.

There are three sets of symmetries a molecule like carbon, with four valences can have. If all four bonds are to identical atoms, the set of symmetries include many planes and axes of rotational symmetry through the molecule. In fact, the molecule is three dimensionally symmetrical. If three bonds are the same and one is different, three planes of symmetry and one axis of rotational symmetry exist in the molecule. If only two bonds are to identical atoms, only a single plane of symmetry exists, and it bisects the two different atoms. Because there is no rotational symmetry in the latter case, there is only one way the molecule can bind to a surface that recognizes three components (as is the case with aconitase). The molecule cannot rotate to another position to enable a different binding. It is for this reason that the symmetric molecule, isocitrate, yields only one specific stereoisomer upon binding with the enzyme aconitase.

See also: Aconitase