Human mitochondrial malate dehydrogenase / MDH2: molecular mechanisms & dependencies

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

Human evidence only

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

Where it participates (unsigned role)

Loss of shuttle components reduced pyruvate/lactate ratios and glucose-derived serine synthesis in the studied human A549 models.
Genetic loss of shuttle components in human A549 cells → Glucose-derived serine synthesis in human A549 cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract and primary figure descriptions
experimental_model
Human lung-cancer cell gene editing, metabolite ratios and carbon tracing.
limitations
A ratio is a redox proxy, and no dietary serine/aspartate deficiency threshold was measured.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Redox handling connects aspartate machinery to synthesis of another amino acid.
primary_references
Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 234–240
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human lung-cancer cell gene editing, metabolite ratios and carbon tracing. · source_derived_draft · unverified_draft
## l-aspartate-shuttle-serine-link Redox handling connects aspartate machinery to synthesis of another amino acid. Loss of shuttle components reduced pyruvate/lactate ratios and glucose-derived serine synthesis in the studied human A549 models. Model: Human lung-cancer cell gene editing, metabolite ratios and carbon tracing. Limitations: A ratio is a redox proxy, and no dietary serine/aspartate deficiency threshold was measured. Evidence access: Primary abstract and primary figure descriptions Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004
Complete structured claim and evidence
Of four benzimidazole anthelmintics tested on purified cytoplasmic and mitochondrial malate dehydrogenase from Ascaris suum, Fasciola hepatica and Moniezia expansa, mebendazole exhibited the highest percentage inhibitions, and the authors conclude that cytoplasmic and mitochondrial malate dehydrogenase regulating glycogen synthesis are the sites of mebendazole inhibitory activity while the sites for the other anthelmintics remain unclear.
Mebendazole → Cytoplasmic and mitochondrial malate dehydrogenase of helminths source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/mebendazole-research/3617430.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "addd86672cc2c829b72354c05387892908f94c49f81e1236e372432c68a622fe", "start_char": 0, "end_char": 589, "text_sha256": "addd86672cc2c829b72354c05387892908f94c49f81e1236e372432c68a622fe"}
experimental_model
Inhibition assays on purified cytoplasmic and mitochondrial malate dehydrogenase from three helminths
exposure
Albendazole, parbendazole, mebendazole and thiabendazole on purified enzyme extracts
limitations
A competing target claim. Enzyme inhibition percentages in purified extracts do not establish that this happens at therapeutic concentrations in a living parasite.
nutrient_topic
Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. · Mebendazole
organism
Helminth
plain_language
A rival account: the drug jams an enzyme of the worm’s sugar metabolism, and mebendazole does it hardest.
primary_references
[mbz-p3617430] Inhibition of malate dehydrogenase enzymes by benzimidazole anthelmintics. (1987). https://pubmed.ncbi.nlm.nih.gov/3617430/ DOI: 10.1016/0304-4017(87)90048-3
tissue_or_cell_type
Ascaris suum, Fasciola hepatica and Moniezia expansa
Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 238–249
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inhibition assays on purified cytoplasmic and mitochondrial malate dehydrogenase from three helminths · source_derived_draft · unverified_draft
### mbz-inhibits-malate-dehydrogenase Of four benzimidazole anthelmintics tested on purified cytoplasmic and mitochondrial malate dehydrogenase from Ascaris suum, Fasciola hepatica and Moniezia expansa, mebendazole exhibited the highest percentage inhibitions, and the authors conclude that cytoplasmic and mitochondrial malate dehydrogenase regulating glycogen synthesis are the sites of mebendazole inhibitory activity while the sites for the other anthelmintics remain unclear. Condition category: normal nutrient_topic: Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. plain_language: A rival account: the drug jams an enzyme of the worm’s sugar metabolism, and mebendazole does it hardest. organism: Helminth tissue_or_cell_type: Ascaris suum, Fasciola hepatica and Moniezia expansa experimental_model: Inhibition assays on purified cytoplasmic and mitochondrial malate dehydrogenase from three helminths limitations: A competing target claim. Enzyme inhibition percentages in purified extracts do not establish that this happens at therapeutic concentrations in a living parasite. exposure: Albendazole, parbendazole, mebendazole and thiabendazole on purified enzyme extracts evidence_span: {"source_cache": "artifacts/mebendazole-research/3617430.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "addd86672cc2c829b72354c05387892908f94c49f81e1236e372432c68a622fe", "start_char": 0, "end_char": 589, "text_sha256": "addd86672cc2c829b72354c05387892908f94c49f81e1236e372432c68a622fe"} [mbz-p3617430] Inhibition of malate dehydrogenase enzymes by benzimidazole anthelmintics. (1987). https://pubmed.ncbi.nlm.nih.gov/3617430/ DOI: 10.1016/0304-4017(87)90048-3
Complete structured claim and evidence

The events it takes part in

A mechanism often involves more than two components. These are the full events, with every participant and its role.

Situations it appears in

Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

Open hypotheses

Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.

This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

Human mitochondrial malate dehydrogenase / MDH2