Triosephosphate isomerase (TIM/TPI; EC 5.3.1.1), a cytosolic glycolytic/gluconeogenic enzyme that catalyzes the reversible, stereospecific, cofactor-independent interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (G3P) via an enediol(ate) intermediate. The enzyme is a catalytically near-perfect, diffusion-limited homodimer adopting the canonical (beta/alpha)8 TIM-barrel fold, with a conserved catalytic glutamate acting as the general base and a histidine as the electrophile. By equilibrating the triose-phosphate pool, TIM links the glycerone-phosphate and glyceraldehyde-3-phosphate branches of central carbon metabolism. In Pseudomonas putida KT2440, whose glucose catabolism is dominated by periplasmic oxidation and the Entner-Doudoroff pathway, triosephosphate isomerase nonetheless participates in an integrated ED/EMP/pentose-phosphate cycle, and is required for growth on both glycolytic (glucose) and gluconeogenic (succinate) carbon sources.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004807 triose-phosphate isomerase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core molecular function. TIM catalyzes the reversible isomerization of DHAP and D-glyceraldehyde 3-phosphate (RHEA:18585, EC:5.3.1.1). Reason: Strongly supported by sequence/family evidence (TIM-barrel fold, conserved catalytic His95 electrophile and Glu167 proton acceptor) and consistent with UniProt/HAMAP-Rule MF_00147. This is the defining catalytic activity of the gene product. Supporting Evidence: file:PSEPK/tpiA/tpiA-deep-research-falcon.md TIM/TPI catalyzes the reversible, stereospecific isomerization of DHAP and D-glyceraldehyde 3-phosphate; conserved catalytic His95 electrophile and Glu167 proton acceptor. PMID:26350459 Deletion of tpiA (PP_4715) abolishes growth of KT2440 on both glucose and succinate, demonstrating an essential triose-phosphate isomerase role. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasmic localization, consistent with a soluble central-carbon-metabolism enzyme lacking signal/transmembrane features. Reason: TIM is a canonical cytosolic enzyme; the more specific cytosol annotation (GO:0005829) is also present. Both are biologically appropriate; cytoplasm is retained as the parent term. |
| GO:0005829 cytosol | IEA GO_REF:0000118 | ACCEPT | Summary: Cytosolic localization, the more specific (preferred) cellular component for this soluble enzyme. Reason: Appropriate and more informative than the parent cytoplasm term; consistent with the soluble homodimeric nature of bacterial TIM. |
| GO:0006094 gluconeogenesis | IEA GO_REF:0000120 | ACCEPT | Summary: TIM provides the DHAP<->G3P interconversion step required for gluconeogenesis; UniProt lists gluconeogenesis as the primary pathway (UPA00138). Reason: Core biological process. Supported experimentally in KT2440 where a tpiA deletion abolishes growth on the gluconeogenic substrate succinate, demonstrating an essential role in gluconeogenic triose-phosphate flux. |
| GO:0006096 glycolytic process | IEA GO_REF:0000120 | ACCEPT | Summary: TIM catalyzes the triose-phosphate isomerization step of glycolysis (UPA00109, step 1/1 G3P from glycerone phosphate). Reason: Core biological process. In KT2440 a tpiA deletion abolishes growth on glucose, confirming an essential role in triose-phosphate balancing within the organism's ED/EMP/PP carbon cycle, despite the atypical (ED-dominated) glucose catabolism. |
| GO:0019563 glycerol catabolic process | IEA GO_REF:0000118 | KEEP AS NON CORE | Summary: Glycerol catabolism feeds into central metabolism via DHAP, which TIM converts to G3P; a plausible downstream role. Reason: This TreeGrafter/PANTHER inference reflects TIM acting on the DHAP produced during glycerol breakdown rather than a glycerol-specific function. The activity is the same generic DHAP<->G3P isomerization already captured by the glycolysis/gluconeogenesis annotations; retain as a non-core specialization rather than a defining process. |
| GO:0046166 glyceraldehyde-3-phosphate biosynthetic process | IEA GO_REF:0000118 | KEEP AS NON CORE | Summary: TIM produces G3P from DHAP, the directionality emphasized by the gluconeogenesis/glycerol-utilization context. Reason: A directional restatement (DHAP -> G3P) of the same reversible isomerization captured by the triose-phosphate isomerase activity and glycolysis/gluconeogenesis annotations. Biologically correct but redundant with the core terms; retain as non-core. |
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