Triose Phosphate Isomerase
From Proteopedia
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== Overview == | == Overview == | ||
| - | '''Triose Phosphate Isomerase''' (TPI or TIM) 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). | + | '''Triose Phosphate Isomerase''' (TPI or TIM) 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). 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. |
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=== Acid Base Catalysis === | === Acid Base Catalysis === | ||
| - | TPI carries out the isomerization reaction through acid base chemistry involving <scene name='Triose_Phosphate_Isomerase/Three_catalytic_residues/1'>three catalytic residues </scene>. First the PGA molecule is held in place by <scene name='Triose_Phosphate_Isomerase/Lys12/1'>Lysine 12</scene>, which provides a positive charge to the active site. <scene name='Triose_Phosphate_Isomerase/Glu165/2'>Glutamate 165</scene>, which plays the role of the general base catalyst in a proton abstraction mechanism , abstracts a proton from carbon 1, which then donates it to carbon 2. Glutamate 165 requires <scene name='Triose_Phosphate_Isomerase/His95/4'>Histidine 95</scene> , the general acid | + | TPI carries out the isomerization reaction through acid base chemistry involving <scene name='Triose_Phosphate_Isomerase/Three_catalytic_residues/1'>three catalytic residues </scene>. First the PGA molecule is held in place by <scene name='Triose_Phosphate_Isomerase/Lys12/1'>Lysine 12</scene>, which provides a positive charge to the active site. <scene name='Triose_Phosphate_Isomerase/Glu165/2'>Glutamate 165</scene>, which plays the role of the general base catalyst in a proton abstraction mechanism , abstracts a proton from carbon 1, which then donates it to carbon 2. However, the carboxylate group of Glutamate 165 alone is not basic enough to abstract a proton requires <scene name='Triose_Phosphate_Isomerase/His95/4'>Histidine 95</scene> , the general acid, to donate a proton to stabilize the negative charge which develops on the C-2 carbonyl group. |
== Structure & Function == | == Structure & Function == | ||
| - | Triose Phosphate Isomerase is part of the all alpha and beta(a/b)class of proteins and it is a dimer consisting of two identical subunits. Each subunit contains <scene name='Triose_Phosphate_Isomerase/Helices/1'>8 exterior alpha helices</scene> surrounding 8 interior <scene name='Triose_Phosphate_Isomerase/Beta_sheet/1'>beta sheets</scene>, which form a structural motif called an closed alpha/beta barrel or more specifically a <scene name='Triose_Phosphate_Isomerase/Tim_barrel/3'>TIM Barrel</scene>. Characteristic of most all alpha/beta barrel domains, the active site is located in a similar position, in the loop regions created by the eight loops that connect the C-terminus of the beta strands with the N-terminus of the alpha helices. | + | Triose Phosphate Isomerase is part of the all alpha and beta(a/b)class of proteins and it is a dimer consisting of two identical subunits. Each subunit contains <scene name='Triose_Phosphate_Isomerase/Helices/1'>8 exterior alpha helices</scene> surrounding 8 interior <scene name='Triose_Phosphate_Isomerase/Beta_sheet/1'>beta sheets</scene>, which form a structural motif called an closed alpha/beta barrel or more specifically a <scene name='Triose_Phosphate_Isomerase/Tim_barrel/3'>TIM Barrel</scene>. Characteristic of most all alpha/beta barrel domains, the active site is located in a similar position, in the loop regions created by the eight loops that connect the C-terminus of the beta strands with the N-terminus of the alpha helices. Upon substrate binding, a loop closes off the active site. |
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Triose Phosphate Isomerase [[http://en.wikipedia.org/wiki/Triosephosphate_isomerase]] | Triose Phosphate Isomerase [[http://en.wikipedia.org/wiki/Triosephosphate_isomerase]] | ||
Triose Phosphate Isomerase Deficiency [[http://en.wikipedia.org/wiki/Triose_Phosphate_Isomerase_deficiency]] | Triose Phosphate Isomerase Deficiency [[http://en.wikipedia.org/wiki/Triose_Phosphate_Isomerase_deficiency]] | ||
| + | Biochemistry 6th Edition (2007)Jeremy M. Berg, John L. Tymoczko, Lubert Stryer | ||
| + | Introduction to Protein Structure Second Edition. Carl Branden & John Tooze | ||
Revision as of 14:11, 22 March 2009
Contents |
Overview
Triose Phosphate Isomerase (TPI or TIM) catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate , an essential process in the glycolytic pathway. More simply, the enzyme catalyzes the isomerization of a ketose (DHAP) to an aldose (GAP). 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.
Mechanism
TPI catalyzes the transfer of a hydrogen atom from carbon 1 to carbon 2, an intramolecular oxidation-reduction. This isomerization of a ketose to an aldose proceeds through an enediol intermediate.
Acid Base Catalysis
TPI carries out the isomerization reaction through acid base chemistry involving . First the PGA molecule is held in place by , which provides a positive charge to the active site. , which plays the role of the general base catalyst in a proton abstraction mechanism , abstracts a proton from carbon 1, which then donates it to carbon 2. However, the carboxylate group of Glutamate 165 alone is not basic enough to abstract a proton requires , the general acid, to donate a proton to stabilize the negative charge which develops on the C-2 carbonyl group.
Structure & Function
Triose Phosphate Isomerase is part of the all alpha and beta(a/b)class of proteins and it is a dimer consisting of two identical subunits. Each subunit contains surrounding 8 interior , which form a structural motif called an closed alpha/beta barrel or more specifically a . Characteristic of most all alpha/beta barrel domains, the active site is located in a similar position, in the loop regions created by the eight loops that connect the C-terminus of the beta strands with the N-terminus of the alpha helices. Upon substrate binding, a loop closes off the active site.
Disease
Triose Phosphate Isomerase Deficiency
TPI deficiency has been most closely linked to a point mutation at the residue which results in the Glu104Asp 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.
References
Triose Phosphate Isomerase [[1]] Triose Phosphate Isomerase Deficiency [[2]] Biochemistry 6th Edition (2007)Jeremy M. Berg, John L. Tymoczko, Lubert Stryer Introduction to Protein Structure Second Edition. Carl Branden & John Tooze
Proteopedia Page Contributors and Editors (what is this?)
Gregg Snider, Eric Martz, Michal Harel, Alexander Berchansky, David Canner, Eran Hodis, Stephen Everse, Angel Herraez, Jane S. Richardson
