Introduction

          TIM has been the subject of many studies ranging from catalytic efficiency to drug design .  TIM has been shown to be a very efficient catalyst, in fact according to Knowles J. R. and company the efficiency value for the interconversion of DHAP and GAP is 0.6 * 10^-11(ii).  Also in his 1977 study he shows that TIM can enoliate 2 * 10³ molecules of DHAP per second as well as isomerate 4 * 10⁸ molecules of GAP (the reverse reaction) per second (iii).  The isomeration reaction limiting step is basically the speed at which a substrate can find the enzyme.  This speed approaches the rate of diffusion (the rate at which molecules bump into each other). In other words this enzyme is fast.  In his study Knolwes proposes that the reason for TIM's speed is evolutionary pressure.  TIM's "job" is to convert DHAP to GAP.  GAP is the molecule that moves on in glycolysis to produce one ATP.  With out TIM DHAP would be a waste product and its energy contribution would be lost.  However because of TIM  DHAP is converted to GAP and approximately three ATPs are produce per glucose instead of one.  Evolutionarily speaking the need for energy in the form of ATP is great.  Knolwes put it best when saying "Since for flight or fight there is an instant requirement for muscle ATP.  We expect that TIM may be a good candidate for a very efficient enzyme, in both the rabbit and the fox that pursues it" (iii).   Knowels theory on evolutionary pressure has become widely accepted and TIM is now known for having nearly reached catalytic perfection.

          TIM has also been the subject of a study involving malaria and sleeping sickness(i).  Trypanosoma brucei is a parasites that has the ability to live in the mammalian bloodstream.  The main source of energy for this parasite is blood sugar. This parasite is the causative agent of sleeping sickness(i). T. brucei, like all other known organisms, has TIM as part of its glycolytic pathway.  The idea was to take advantage of the differences between human and T. brucei TIM as a way of eliminating T. brucei from the bloodstream.  If some one could come up with a substrate that would irreversibly bind only T. brucei TIM that would shut down glycolysis thus removing the parasite.  First, however the correct structure of T. brucei TIM must be known and that was the main focus of the two references I have sighted (i) and  (iv).