Triose Phosphate Isomerase

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Contents 1 Overview 2 Mechanism 2.1 Acid Base Catalysis 3 Structure & Function 4 Disease 4.1 Triose Phosphate Isomerase Deficiency 5 References

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