Evidence map›Paper›PMID 39519689›Full record

ArticleMolecules (Basel, Switzerland)2024

Methylglyoxal-Induced Modifications in Human Triosephosphate Isomerase: Structural and Functional Repercussions of Specific Mutations.

Ignacio de la Mora-de la Mora, Itzhel García-Torres, Luis Antonio Flores-López, Gabriel López-Velázquez, Gloria Hernández-Alcántara, Saúl Gómez-Manzo, Sergio Enríquez-Flores

Abstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Ignacio de la Mora-de la MoraLaboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.ORCID 0000-0002-5654-8089
Itzhel García-TorresLaboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.
Luis Antonio Flores-LópezLaboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.ORCID 0000-0002-2332-4361
Gabriel López-VelázquezLaboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.ORCID 0000-0003-0470-1069
Gloria Hernández-AlcántaraDepartamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City 04510, Mexico.ORCID 0000-0002-7029-6033
Saúl Gómez-ManzoLaboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.ORCID 0000-0003-2095-9182
Sergio Enríquez-FloresLaboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico.ORCID 0000-0003-2058-5707

Funding

Consejo Nacional de Humanidades, Ciencias y Tecnologías Ciencia de Frontera CF-2023-1-811Instituto Nacional de Pediatria 2019/072 (S.E.-F.)Recursos Fiscales para la Investigación 2020/016 (L.A.F.-L.)
6 · The paper itself

Abstract

Triosephosphate isomerase (TPI) dysfunction is a critical factor in diverse pathological conditions. Deficiencies in TPI lead to the accumulation of toxic methylglyoxal (MGO), which induces non-enzymatic post-translational modifications, thus compromising protein stability and leading to misfolding. This study investigates how specific TPI mutations (E104D, N16D, and C217K) affect the enzyme's structural stability when exposed to its substrate glyceraldehyde 3-phosphate (G3P) and MGO. We employed circular dichroism, intrinsic fluorescence, native gel electrophoresis, and Western blotting to assess the structural alterations and aggregation propensity of these TPI mutants. Our findings indicate that these mutations markedly increase TPI's susceptibility to MGO-induced damage, leading to accelerated loss of enzymatic activity and enhanced protein aggregation. Additionally, we observed the formation of MGO-induced adducts, such as argpyrimidine (ARGp), that contribute to enzyme inactivation and aggregation. Importantly, the application of MGO-scavenging molecules partially mitigated these deleterious effects, highlighting potential therapeutic strategies to counteract MGO-induced damage in TPI-related disorders.

Indexed as

PyruvaldehydeTriose-Phosphate IsomeraseAnemia, Hemolytic, Congenital NonspherocyticCarbohydrate Metabolism, Inborn ErrorsKineticsLoss of Function MutationProtein ConformationSpectrum AnalysisPyruvaldehydeTriose-Phosphate Isomerasecatalytic agingconformational changesenzymatic rescuemolecular dockingmolecular dysfunctionmolecular wearprotein structure–function relationshipspectroscopic analysis

Identifiers

PMID39519689
PMCPMC11547674

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.