Triose Phosphate Isomerase: Difference between revisions

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Gregg Snider, Stephen Everse, Eran Hodis, David Canner, Eric Martz, Michal Harel, Alexander Berchansky, Jane S. Richardson, Angel Herraez

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 == Disease ==
 {{STRUCTURE_2ypi|  PDB=2ypi  |  SCENE=Triose_Phosphate_Isomerase/Glu104/1}}
-[http://en.wikipedia.org/wiki/Triose_Phosphate_Isomerase_deficiency Triose Phosphate Isomerase Deficiency], initially described in 1965, is an autosomal recessive inherited disorder with characteristics ranging from chronic haemolytic anaemia, increased susceptibility to infections, severe neurological dysfunction, and often times death in early childhood.<ref>PMID:10916682</ref> TPI has been most closely linked to a point mutation at the <scene name='Triose_Phosphate_Isomerase/Glu_104/3'>Glu104</scene> residue which results in the <scene name='Triose_Phosphate_Isomerase/Glu104asp2/1'>Glu104Asp</scene> mutation. A common marker for TPI deficiency is the increased accumulation of dihydroxyacetone phosphate in erythrocyte extracts as a result in the inability of the mutant enzyme to catalyze the isomerization to D-glyceraldehyde-3-phosphate. Recent evidence has indicated that the point mutation does not prove detrimental to the rate of catalysis of the enzyme, but rather effects the ability of the enzyme to dimerize.<ref>PMID:17183658</ref>
+<ref>http://en.wikipedia.org/wiki/Triose_Phosphate_Isomerase_deficiency Triose Phosphate Isomerase Deficiency<ref>, initially described in 1965, is an autosomal recessive inherited disorder with characteristics ranging from chronic haemolytic anaemia, increased susceptibility to infections, severe neurological dysfunction, and often times death in early childhood.<ref>PMID:10916682</ref> TPI has been most closely linked to a point mutation at the <scene name='Triose_Phosphate_Isomerase/Glu_104/3'>Glu104</scene> residue which results in the <scene name='Triose_Phosphate_Isomerase/Glu104asp2/1'>Glu104Asp</scene> mutation. A common marker for TPI deficiency is the increased accumulation of dihydroxyacetone phosphate in erythrocyte extracts as a result in the inability of the mutant enzyme to catalyze the isomerization to D-glyceraldehyde-3-phosphate. Recent evidence has indicated that the point mutation does not prove detrimental to the rate of catalysis of the enzyme, but rather effects the ability of the enzyme to dimerize.<ref>PMID:17183658</ref>
 '''Role in Alzheimer's Disease''': Recent discoveries in Alzheimer Disease research has indicated that amyloid beta-peptide induced nitro-oxidative damage promotes the nitrotyrosination of the glycolytic enzyme triosephosphate isomerase in human neuroblastoma cells.<ref>PMID:19251756</ref> nitro-triosephosphate isomerase was found to be present in brain slides from double transgenic mice overexpressing human amyloid precursor protein as well as in Alzheimer's disease patients. Specifically, the nitrotyrosination occurs on <scene name='Triose_Phosphate_Isomerase/Two_tyrosines_shaded/2'>Tyr164 and Tyr208</scene> , which are located in close proximity to the catalytic center, and this modification correlates with a reduced isomerase activity. Additionally, according to work done by Francesc Guix and colleagues, nitro-triosphosphate isomerase contributed to the formation of large beta-sheet aggregates ''in vitro'' and ''in vivo''.