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Triosephosphate isomerase deficiency: New insights into an enigmatic disease
- Source :
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1792(12):1168-1174
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- 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.
- Subjects :
- Isomerase
Pentose phosphate pathway
Biology
Triosephosphate isomerase
Animals, Genetically Modified
chemistry.chemical_compound
Mice
Glycation
Methylglyoxal
medicine
Animals
Animal model
Neurodegeneration
Enzymopathy
Advanced glycation end products (AGEs)
Triosephosphate isomerase deficiency
Molecular Biology
Dihydroxyacetone phosphate
chemistry.chemical_classification
Conformational disease
Aldolase A
Anemia, Hemolytic, Congenital Nonspherocytic
medicine.disease
Enzyme
chemistry
Biochemistry
Oxidative stress
biology.protein
Molecular Medicine
Drosophila
Glycolysis
Triose-Phosphate Isomerase
Subjects
Details
- ISSN :
- 09254439
- Volume :
- 1792
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Accession number :
- edsair.doi.dedup.....f9aa2133624ba69ad912deecc5c8ef4c
- Full Text :
- https://doi.org/10.1016/j.bbadis.2009.09.012