|Figure 1. Glycolysis pathway highlighting TIM role (Figure 14-2 from Leighner)|
|Figure 2. Isomerization reaction by TIM from SigmaAldrich|
|Figure 3. Enediolate and sulfate bound to Triose phosphate isomerase (3PY2)|
Lack-of-function mutations (most commonly E104D) cause a serious, progressive, neurological disease creatively entitled triose phosphate isomerase deficiency...yep, creative. The most common characteristic of this disease is hemolytic anemia--the abnormal breakdown of red blood cells.
Trypanosoma brucei, the parasite that causes African sleeping sickness, also has this enzyme. However, it has an extra 22-amino acid fragment that is unique. It has been found to send responder signals to glycosomes: a subset of peroxisomes. This same TIM protein with the extra 22-amino acid fragment was put into a similar organism and it did not target the glycosomes. This presents a potential drug target for African sleeping sickness. It is, quite surprisingly, found in an enzyme shared by most organisms.
Galland, N., de Walque, S., Voncken, F.G., Verlinde, C.L., Michels, P.A. “An internal sequence targets Trypanosoma brucei triosephosphate isomerase to glycosomes” Mol Biochem Parasitol 171.1 May (2010): 45-49. Medline. Wed. 28 Apr. 2011.
Orosz, F., Oláh, J. and Ovádi, J. (2006), Triosephosphate isomerase deficiency: Facts and doubts. IUBMB Life, 58: 703–715. doi: 10.1080/15216540601115960
Wierenga, R K., E G. Kapetaniou, and R Venkatesan. "Triosephosphate isomerase: a highly evolved biocatalyst." Cell Mol Life Sci67.237 Aug. (2010): 3961-82. Medline. Web. 28 Apr. 2011.