p(INTERPRO:"Triosephosphate isomerase")

Entity

Name

Triosephosphate isomerase

Namespace

interpro

Namespace Version

20181021

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/f2f993e599694ab5ce989cc39d789a499f75db99/external/interpro-names.belns

Tau Modifications Sections of NESTOR

In accordance with the decreased efficiency of nitro-TPI we found a significant increase in methylglyoxal production (P50.05), independent of whether DHAP or GAP was used as substrate (Fig. 2E). Thus, nitrotyrosination of TPI results in reduced catalytic activity and increased occupancy of the enzyme by the substrate, and consequently, a higher production of the toxic methylglyoxal. PubMed:19251756

Triosephosphate isomerase (TPI) is a key enzyme in cell metabolism that controls the glycolytic flow and energy production through the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (G3P) (Richard, 1993). Notably, TPI is the only glycolytic enzyme whose functional deficiency is associated to neurodegeneration (Eber et al., 1991; Ovadi et al., 2004). In particular, inefficient glycolysis (Hoyer et al., 1988) and ATP depletion (Keil et al., 2004) are characteristic in Alzheimer’s disease brains. PubMed:19251756

Nitration of Tyr164 and Tyr208 would destabilize the closed state of loop 6 because the interaction between Tyr208 and Ala176 through an H-bond would be compromised (Fig. 2A and B; Supplementary Fig. S2). Indeed, purified TPI after nitrotyrosination with a peroxynitrite donor (SIN-1) displayed a significant decrease in isomerase activity in both directions of the catalysis, i.e. using DHAP (Fig. 2C) or GAP (Fig. 2D) as substrate. PubMed:19251756

Nitration of Tyr164 and Tyr208 would destabilize the closed state of loop 6 because the interaction between Tyr208 and Ala176 through an H-bond would be compromised (Fig. 2A and B; Supplementary Fig. S2). Indeed, purified TPI after nitrotyrosination with a peroxynitrite donor (SIN-1) displayed a significant decrease in isomerase activity in both directions of the catalysis, i.e. using DHAP (Fig. 2C) or GAP (Fig. 2D) as substrate. PubMed:19251756

Triosephosphate isomerase (TPI) is a key enzyme in cell metabolism that controls the glycolytic flow and energy production through the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (G3P) (Richard, 1993). Notably, TPI is the only glycolytic enzyme whose functional deficiency is associated to neurodegeneration (Eber et al., 1991; Ovadi et al., 2004). In particular, inefficient glycolysis (Hoyer et al., 1988) and ATP depletion (Keil et al., 2004) are characteristic in Alzheimer’s disease brains. PubMed:19251756

Triosephosphate isomerase (TPI) is a key enzyme in cell metabolism that controls the glycolytic flow and energy production through the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (G3P) (Richard, 1993). Notably, TPI is the only glycolytic enzyme whose functional deficiency is associated to neurodegeneration (Eber et al., 1991; Ovadi et al., 2004). In particular, inefficient glycolysis (Hoyer et al., 1988) and ATP depletion (Keil et al., 2004) are characteristic in Alzheimer’s disease brains. PubMed:19251756

In accordance with the decreased efficiency of nitro-TPI we found a significant increase in methylglyoxal production (P50.05), independent of whether DHAP or GAP was used as substrate (Fig. 2E). Thus, nitrotyrosination of TPI results in reduced catalytic activity and increased occupancy of the enzyme by the substrate, and consequently, a higher production of the toxic methylglyoxal. PubMed:19251756