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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 {{STRUCTURE_2ypi|PDB=2ypi|SCENE=}}
-[[Triose Phosphate Isomerase]] (TPI or TIM) [5.3.1.1] is a ubiquitous enzyme with a molecular weight of roughly 54 kD (27 kD per subunit) which catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate DHAP and D-glyceraldehyde-3-phosphate <scene name='Triose_Phosphate_Isomerase/Pga/1'>(GAP)</scene>, 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. 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 only limited by the substrate diffusion rate. Diffusion as the rate-limiting step was experimentally confirmed through the use of viscogens such as glycerol and sucrose. Other catalytically perfect enzymes include carbonic anhydrase, acetylcholinesterase, catalase, and fumarase. In addition to its relevance in glycolysis, TPI is also involved in several additional metabolic biological processes including gluconeogenesis, the pentose phosphate shunt, and fatty acid biosynthesis.
+[[Triose Phosphate Isomerase]] (TPI or TIM) [5.3.1.1] is a ubiquitous dimeric enzyme with a molecular weight of roughly 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 GAP, 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. Diffusion as the rate-limiting step was experimentally confirmed through the use of viscogens such as glycerol and sucrose. Other catalytically perfect enzymes include carbonic anhydrase, acetylcholinesterase, and catalase. 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.
 == Mechanism ==