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Last update 08 May 2025

TPI1

Last update 08 May 2025

Basic Info

Synonyms

Methylglyoxal synthase, TIM, TPI

+ [4]

Introduction

It is also responsible for the non-negligible production of methylglyoxal a reactive cytotoxic side-product that modifies and can alter proteins, DNA and lipids. Triosephosphate isomerase is an extremely efficient metabolic enzyme that catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis and gluconeogenesis.

Drugs associated with TPI1

CN117586405

Patent Mining

Target

TPI1

Mechanism-

Active Org.

Lanzhou University

Originator Org.

Lanzhou University

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

RT-001(RetinaPharma)

Target

TPI1

Mechanism

TPI1 inhibitors

Active Org.-

Originator Org.

RetinaPharma Technologies, Inc.

Active Indication-

Inactive Indication

Glaucoma [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TPI1

100 Translational Medicine associated with TPI1

0 Patents (Medical) associated with TPI1

3,081

Literatures (Medical) associated with TPI1

31 Dec 2025·Artificial Cells, Nanomedicine, and Biotechnology

IRES activation: HK2 and TPI1 glycolytic enzymes play a pivotal role in non-neuronal cell survival under hypoxia

Article

Author: Devi, Sushma ; Hussain, Mahboob-Ul- ; Arora, Poonam ; Rahamathulla, Mohamed ; Banday, Muddasir Sharief ; Kumar, Manish ; Shivanandappa, Thippeswamy Boreddy ; Najar, Imtiyaz Ahmed ; Pasha, Ismail ; Ismail, Rehana ; Ahmed, Mohammed Muqtader

Hypoxia-induced brain damage can cause consciousness, memory failure and death. HK2 and TPI1 were investigated to see how they change hypoxia sensitivity in neurons and non-neurons. Hypoxia sensitivity is determined by the differential overexpression of both important glycolytic enzymes in neuronal and non-neuronal cells. C6 glioma cells expressed greater HK2 and TPI1 protein than neuro 2A cells, which were more sensitive to hypoxia-induced cell death by MTT and lactate dehydrogenase leakage assay. After 48 h of hypoxia, C6 glioma cells displayed substantial protein upregulation of HK2 and TPI1 glycolytic proteins but not mRNA. Hypoxia did not raise HK2 and TPI1 mRNA transcription, pointing at post-transcriptional protein regulation. Using di-cistronic and promoter-less di-cistronic assays, we discovered significant IRES regions in HK2 and TPI1 mRNA's 5'UTR, more active in C6 glioma cells with polypyrimidine tract binding (PTB) protein. We concluded that non-neuronal cells varied in HK2 and TPI1 overexpression, altering their vulnerability to hypoxia-induced cell death. Adjusting HK2, TP1 and PTB levels may prevent hypoxia-induced brain cell death. These results offer new information on glycolytic enzyme modulation under hypoxia, crucial for comprehending cell survival in hypoxic situations. This could affect situations like neurodegenerative illnesses or ischaemic injuries, where hypoxia-induced cell death is crucial.

01 Jul 2025·Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

Role of electrostatics in cold adaptation: A comparative study of eury- and stenopsychrophilic triose phosphate isomerase

Article

Author: Nowak, Jan S ; Brodersen, Ditlev E ; Olesen, Sune ; Otzen, Daniel E ; Tian, Pengfei ; Bærentsen, René L

Psychrophilic (cold-active) organisms have developed enzymes that facilitate sufficient metabolic activity at low temperatures to sustain life. This occurs through molecular adaptations that tend to increase protein flexibility at the expense of stability. However, psychrophiles also vary in their growth conditions. Eurypsychrophiles thrive over a wide temperature range and often prefer temperatures above 20 °C, while stenopsychrophiles grow optimally below 15 °C and are more narrowly adapted to cold temperatures. To elucidate differences between these two classes of enzymes, we here compare the stability and unfolding kinetics of two orthologues of the basal household enzyme triose phosphate isomerase, one from the stenopsychrophilic Antarctic permafrost bacterium Rhodonellum psychrophilum (sTPI) and the other from the eurypsychrophilic Greenland ikaite column bacterium Rhodococcus sp. JG-3 (eTPI). Remarkably, sTPI proved significantly more thermostable and resistant to chemical denaturation than its eurypsychrophilic counterpart, eTPI, in the absence of ionic components in solution, whereas inclusion of electrostatic screening agents in the form of sodium chloride or the charged denaturant guanidinium chloride largely cancelled out this difference. Thus, electrostatics play a prominent role in stabilizing the stenopsychrophilic sTPI, and a mandatory low-temperature growth environment does not preclude the development of considerable thermotolerance for individual enzymes. We were able to increase the thermostability of sTPI using an evolutionary machine learning model, which transferred several sTPI residues into the eTPI active site. While the stabilizing effect was modest, the combination of individual mutations was additive, underscoring the potential of combining multiple beneficial mutations to achieve enhanced enzyme properties.

01 Jun 2025·Anaerobe

Molecular detection of toxigenic Clostridioides difficile in subgingival biofilm of severe periodontitis

Article

Author: Leite de Oliveira Rosa, Isabela ; de Oliveira Ferreira, Eliane ; Vieira Colombo, Ana Paula

OBJECTIVESThe oral cavity is the main gateway for the entry of C. difficile spores to the digestive tract. In conditions of poor oral hygiene and periodontal diseases, the dysbiotic oral microbiota may be a reservoir for several human pathogens. Here, we explored the prevalence of C. difficile in the oral microbiota of patients with severe periodontitis by the molecular detection of species specific genes.METHODSSubgingival biofilm, saliva and/or feces from 659 patients with gingivitis, periodontitis and no periodontal diseases were screened for the tpi and toxin A/B genes specific for C. difficile by multiplex PCR. Differences among groups were sought by the Chi-square test.RESULTSThe overall frequency of C. difficile tpi gene was 29 %, with a high detection of tcdB gene (44.8 %). Patients with periodontitis showed a greater prevalence of this gene in the biofilm than individuals with gingivitis and periodontal health (p = 0.001), particularly at more severe stages of disease (p < 0.05). No toxin genes were detected in feces or biofilm from healthy patients, whereas >70 % of the biofilm from patients with periodontal diseases were positive for these genes (p < 0.001). Detection of C. difficile tpi gene in oral/fecal samples correlated with periodontal inflammation (p < 0.05). A modest intra-individual agreement between tpi gene detection in feces and saliva was found within periodontitis patients (Kappa = 0.314; p = 0.003).CONCLUSIONThe high frequency of the C. difficile specific genes tpi and tcdB in the dysbiotic subgingival biofilm of advanced periodontitis could support the presence of the bacterium in this niche.

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TPI1

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