Triosephosphate isomerase

Triosephosphate isomerase (TIM) is a glycolytic enzyme encoded by TPI1 that catalyzes the interconversion of dihydroxyacetone phosphate and D-glyceraldehyde-3-phosphate. Beyond its canonical role in energy metabolism, TIM also generates methylglyoxal, a reactive cytotoxic byproduct capable of modifying proteins, DNA, and lipids (UniProt: P60174).

The enzyme is expressed broadly across tissues supporting glycolysis and gluconeogenesis. TPI1 mutations cause triosephosphate isomerase deficiency, a rare autosomal recessive disorder presenting with hemolytic anemia, progressive neurodegeneration, immunodeficiency, and cardiomyopathy (UniProt: P60174), highlighting its critical role in neurological function.

TPI1 is associated with Alzheimer's disease. In post-mortem AD brain tissue analyzed by quantitative proteomics, TPI1 was significantly upregulated compared to age-matched controls (mean log2 fold-change: 0.91), suggesting altered glycolytic capacity and potentially elevated methylglyoxal production in the AD brain (Chaparral AD proteomics).