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Evidence of a triosephosphate isomerase non-catalytic function crucial to behavior and longevity.


ABSTRACT: Triosephosphate isomerase (TPI) is a glycolytic enzyme that converts dihydroxyacetone phosphate (DHAP) into glyceraldehyde 3-phosphate (GAP). Glycolytic enzyme dysfunction leads to metabolic diseases collectively known as glycolytic enzymopathies. Of these enzymopathies, TPI deficiency is unique in the severity of neurological symptoms. The Drosophila sugarkill mutant closely models TPI deficiency and encodes a protein prematurely degraded by the proteasome. This led us to question whether enzyme catalytic activity was crucial to the pathogenesis of TPI sugarkill neurological phenotypes. To study TPI deficiency in vivo we developed a genomic engineering system for the TPI locus that enables the efficient generation of novel TPI genetic variants. Using this system we demonstrate that TPI sugarkill can be genetically complemented by TPI encoding a catalytically inactive enzyme. Furthermore, our results demonstrate a non-metabolic function for TPI, the loss of which contributes significantly to the neurological dysfunction in this animal model.

SUBMITTER: Roland BP 

PROVIDER: S-EPMC3711204 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Evidence of a triosephosphate isomerase non-catalytic function crucial to behavior and longevity.

Roland Bartholomew P BP   Stuchul Kimberly A KA   Larsen Samantha B SB   Amrich Christopher G CG   Vandemark Andrew P AP   Celotto Alicia M AM   Palladino Michael J MJ  

Journal of cell science 20130502 Pt 14


Triosephosphate isomerase (TPI) is a glycolytic enzyme that converts dihydroxyacetone phosphate (DHAP) into glyceraldehyde 3-phosphate (GAP). Glycolytic enzyme dysfunction leads to metabolic diseases collectively known as glycolytic enzymopathies. Of these enzymopathies, TPI deficiency is unique in the severity of neurological symptoms. The Drosophila sugarkill mutant closely models TPI deficiency and encodes a protein prematurely degraded by the proteasome. This led us to question whether enzym  ...[more]

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