Triose Phosphate Isomerase: Difference between revisions
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== Disease == | == Disease == | ||
<Structure load='2ypi' size='300' frame='true' align='right' scene='Triose_Phosphate_Isomerase/Glu_104_1/ | <Structure load='2ypi' size='300' frame='true' align='right' scene='Triose_Phosphate_Isomerase/Glu_104_1/6'/> | ||
'''Triose Phosphate Isomerase Deficiency''': Initially described in 1965, TPI deficiency 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> The effects of TPI deficiency are most closely linked to a point mutation at the <scene name='Triose_Phosphate_Isomerase/Glu_104_1/ | '''Triose Phosphate Isomerase Deficiency''': Initially described in 1965, TPI deficiency 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> The effects of TPI deficiency are most closely linked to a point mutation at the <scene name='Triose_Phosphate_Isomerase/Glu_104_1/6'>Glu104</scene> residue which results in the <scene name='Triose_Phosphate_Isomerase/Glu104asp3/2'>Glu104Asp</scene> mutation. A common marker for TPI deficiency is the increased accumulation of DHAP in erythrocyte extracts as a result in the inability of the mutant enzyme to catalyze the isomerization to GAP. 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 have indicated that amyloid beta-peptide induced nitro-oxidative damage promotes the nitrotyrosination of TPI in human neuroblastoma cells.<ref>PMID:19251756</ref> Nitrosylated TPI was found to be present in brain slides from double transgenic mice over-expressing human amyloid precursor protein as well as in Alzheimer's disease patients. Specifically, the nitrotyrosination occurs on <scene name='Triose_Phosphate_Isomerase/Two_tyrosines_shaded1/1'>Tyr164 and Tyr208</scene> , which are located in close proximity to the catalytic center, and this modification correlates with reduced isomerization activity. Additionally, Francesc Guix and colleagues have shown nitrosylated TPI contributed to the formation of large beta-sheet aggregates ''in vitro'' and ''in vivo''. | '''Role in Alzheimer's Disease''': Recent discoveries in Alzheimer Disease research have indicated that amyloid beta-peptide induced nitro-oxidative damage promotes the nitrotyrosination of TPI in human neuroblastoma cells.<ref>PMID:19251756</ref> Nitrosylated TPI was found to be present in brain slides from double transgenic mice over-expressing human amyloid precursor protein as well as in Alzheimer's disease patients. Specifically, the nitrotyrosination occurs on <scene name='Triose_Phosphate_Isomerase/Two_tyrosines_shaded1/1'>Tyr164 and Tyr208</scene> , which are located in close proximity to the catalytic center, and this modification correlates with reduced isomerization activity. Additionally, Francesc Guix and colleagues have shown nitrosylated TPI contributed to the formation of large beta-sheet aggregates ''in vitro'' and ''in vivo''. | ||