Triosephosphate Isomerase (TIM) is an important enzyme of glycolysis. Glycolysis is the first step in cellular respiration. Glucose is converted to pyruvate and pyruvate enters the Kreb's cycle. During this process TIM catalyzes the interconversion of D-glyceraldhyde 3-phosphate (GAP) and dihydroxyacetone. Fructose 1,6-bisphosphate is cleaved into GAP and DHAP during glycolysis . GAP continues on the glycolitic pathway however DHAP must be converted to GAP before it can continue. TIM is the enzyme that catalyzes this reaction. Glycolysis is believed to be one of the earliest biochemical processes to evolve. Every living thing from bacteria to human is capable of glycolysis. Some parts of the TIM enzyme are highly conserved indicating their importance in the efficiency of the enzymatic activity.

Three point mutations in TIM are the cause of severe genetic diseases. A change of Glu 104 to Asp, Phe 240 to Ile, and Gly 122 to Arg may cause disorders ranging from hemolytic disorder to neuromuscular impairment. Triosephosphate isomerase deficiency usually affects many systems. People suffering with this disorder may suffer progressive neuromuscular dysfunction, Chronic nonspherocytic hemolytic anemia and increased susceptibility to infections. Life expectancy is short, usually less than 6 years(2).

Much research has been put in to determine the structure and function of TIM in an attempt to create drugs against parasitic infections. TIM of Trypoanosoma brucei, the causative agent of sleeping sickness, has been the subject of research in an attempt to create a drug effective against T. brucei with little side effects against humans. This search is made more difficult by the fact many drugs capable of destroying parasites have a detremental effect on the host as well. Differences between human TIM and T. brucei TIM may be exploited to eliminate the parasite from its human host with little injury to the host. One difference that is being explored is an interface Cys 14 that is not present in human TIM. If a way is found to perturb the interface by interaction with this Cys a treatment may be found for T. brucei. Gomez-Puyou et al, used methyl methanethiosulfonate (MMTS) to derivatize Cys 14 to a methyl sulfide. MMTS dramatically inhibited TIM activity in TIMs with a Cys residue at a position 14. This same treatment had a significantly lesser effect on rabbit TIM (20% inhibition) and yeast TIM (negligible.) This effect may open up a new option for species specific inhibition(3).