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(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.<Biochemistry 6th Edition>

Acid Base Catalysis

TPI carries out the isomerization reaction through acid base chemistry involving . These two catalytic residues include which plays the role of the general base catalyst in a proton abstraction mechanism as it 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 a dimeric protein of two identical subunits. Each subunit contains 8 alpha helices surrounding 8 interior , which form a structural motif called an alpha/beta barrel or , which also contain the catalytic residues.

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]]