Triose Phosphate Isomerase

From Proteopedia

Revision as of 02:21, 22 March 2009

Template:STRUCTURE 1tim

Overview

Triose Phosphate Isomerase (TPI or TIM) 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).

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. Glutamate 165 requires , the general acid which donates a proton to the C-1 carbonyl oxygen.

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.

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]]