Triose Phosphate Isomerase: Difference between revisions
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caption='TPI (yeast) at 2.5 Å [[resolution]] ([[2ypi]]). The two identical chains are different colors. Ligand is the inhibitor 2-phosphoglycolic acid (PGA). ' | caption='TPI (yeast) at 2.5 Å [[resolution]] ([[2ypi]]). The two identical chains are different colors. Ligand is the inhibitor 2-phosphoglycolic acid (PGA). ' | ||
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[[Triose Phosphate Isomerase]] (TPI or TIM) is a ubiquitous dimeric enzyme with a molecular weight of ~54 kD (27 kD per subunit) which catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate ('''DHAP''') and D-glyceraldehyde-3-phosphate ('''GAP'''), an essential process in the glycolytic pathway. More simply, the enzyme catalyzes the isomerization of a ketose (DHAP) to an aldose (GAP), also referred to as '''PGAL'''. In regards to the two isomers, at equilibrium, roughly 96% of the triose phosphate is in the DHAP isomer form; however, the isomerization reaction proceeds due to the rapid removal of GAP from the subsequent reactions of glycolysis. The TPI structure is shown on the right (PDB entry [[2ypi]]) in complex with the inhibitor 2-phosphoglycolic acid (PGA), which is bound to each of its two active sites. TPI is an example of a catalytically perfect enzyme, indicating that for almost every enzyme-substrate encounter, a product is formed and that this interaction is limited only by the substrate diffusion rate. | [[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg|thumb|left|260px| Ribbon drawing of the "TIM barrel" fold]] | ||
[[Triose Phosphate Isomerase]] (TPI or TIM) is a ubiquitous dimeric enzyme with a molecular weight of ~54 kD (27 kD per subunit) which catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate ('''DHAP''') and D-glyceraldehyde-3-phosphate ('''GAP'''), an essential process in the glycolytic pathway. More simply, the enzyme catalyzes the isomerization of a ketose (DHAP) to an aldose (GAP), also referred to as '''PGAL'''. In regards to the two isomers, at equilibrium, roughly 96% of the triose phosphate is in the DHAP isomer form; however, the isomerization reaction proceeds due to the rapid removal of GAP from the subsequent reactions of glycolysis. The TPI tertiary structure is the classic example of the "TIM barrel" fold (see image at left). The TPI structure is shown on the right (PDB entry [[2ypi]]) in complex with the inhibitor 2-phosphoglycolic acid (PGA), which is bound to each of its two active sites. TPI is an example of a catalytically perfect enzyme, indicating that for almost every enzyme-substrate encounter, a product is formed and that this interaction is limited only by the substrate diffusion rate. | |||
In addition to its role in glycolysis, TPI is also involved in several additional metabolic biological processes including gluconeogenesis, the pentose phosphate shunt, and fatty acid biosynthesis. A point mutation to a glutamate residue (Glu104) of TPI results in triose phosphate isomerase deficiency, an autosomal recessive inherited disorder characterized by an increased accumulation of DHAP in erythrocytes. Structurally, this point mutation abolishes TPI’s ability to dimerize, subsequently inhibiting its catalytic activity. More details in [[ Triose Phosphate Isomerase Structure & Mechanism]]. | In addition to its role in glycolysis, TPI is also involved in several additional metabolic biological processes including gluconeogenesis, the pentose phosphate shunt, and fatty acid biosynthesis. A point mutation to a glutamate residue (Glu104) of TPI results in triose phosphate isomerase deficiency, an autosomal recessive inherited disorder characterized by an increased accumulation of DHAP in erythrocytes. Structurally, this point mutation abolishes TPI’s ability to dimerize, subsequently inhibiting its catalytic activity. More details in [[ Triose Phosphate Isomerase Structure & Mechanism]]. | ||