Triosephosphate isomerase deficiency: New insights into an enigmatic disease

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The triosephosphate isomerase (TPI) functions at a metabolic cross-road ensuring the rapid equilibration of the triosephosphates produced by aldolase in glycolysis, which is interconnected to lipid metabolism, to glycerol-3-phosphate shuttle and to the pentose phosphate pathway. The enzyme is a stable homodimer, which is catalytically active only in its dimeric form. TPI deficiency is an autosomal recessive multisystem genetic disease coupled with hemolytic anemia and neurological disorder frequently leading to death in early childhood. Various genetic mutations of this enzyme have been identified; the mutations result in decrease in the catalytic activity and/or the dissociation of the dimers into inactive monomers. The impairment of TPI activity apparently does not affect the energy metabolism at system level; however, it results in accumulation of dihydroxyacetone phosphate followed by its chemical conversion into the toxic methylglyoxal, leading to the formation of advanced glycation end products. By now, the research on this disease seems to enter a progressive stage by adapting new model systems such as Drosophila, yeast strains and TPI-deficient mouse, which have complemented the results obtained by prediction and experiments with recombinant proteins or erythrocytes, and added novel data concerning the complexity of the intracellular behavior of mutant TPIs. This paper reviews the recent studies on the structural and catalytic changes caused by mutation and/or nitrotyrosination of the isomerase leading to the formation of an aggregation-prone protein, a characteristic of conformational disorders.

Original languageEnglish
Pages (from-to)1168-1174
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number12
Publication statusPublished - Dec 1 2009



  • Advanced glycation end products (AGEs)
  • Animal model
  • Conformational disease
  • Enzymopathy
  • Glycolysis
  • Methylglyoxal
  • Neurodegeneration
  • Oxidative stress

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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