ReviewJournal of inherited metabolic disease2014
Metabolic biology of 3-methylglutaconic acid-uria: a new perspective.
Review in Journal of inherited metabolic disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Causal proteomic insights into drug target discovery for tension-type headache.The journal of headache and pain · 2025Article
- 3-Methyl Glutaconic Aciduria and Elevated Plasma Growth Differentiation Factor 15 Level in an Adult with MonoallelicActa myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Article
- Small Molecules as Alternate Substrates for 3-Methylglutaconylation.JIMD reports · 2025Article
- Metabolic origin and significance of 3-methylglutaryl CoA.Clinica chimica acta; international journal of clinical chemistry · 2025Review
- YME1L1 Dysfunction Associated With 3-Methylglutaconic Aciduria.Journal of inherited metabolic disease · 2025Article
- Article
- Factors Affecting Non-Enzymatic Protein Acylation byMetabolites · 2024Article
- Perturbations in mitochondrial metabolism associated with defective cardiolipin biosynthesis: AnbioRxiv : the preprint server for biology · 2024Article
- 3-Methylglutarylcarnitine: A biomarker of mitochondrial dysfunction.Clinica chimica acta; international journal of clinical chemistry · 2023Review
- Article
- Characterization ofMetabolites · 2023Article
- Integrated landscape of cardiac metabolism in end-stage human nonischemic dilated cardiomyopathy.Nature cardiovascular research · 2022Article
- N-acetylglutamate synthase deficiency with associated 3-methylglutaconic aciduria: A case report.JIMD reports · 2022Article
- Metabolite Signature of Simvastatin Treatment Involves Multiple Metabolic Pathways.Metabolites · 2022Article
- Beyond predicting diagnosis: Is there a role for measuring biotinidase activity in liver glycogen storage diseases?Molecular genetics and metabolism reports · 2022Article
- Role of non-enzymatic chemical reactions in 3-methylglutaconic aciduria.The FEBS journal · 2022Article
- Diversion of Acetyl CoA to 3-Methylglutaconic Acid Caused by Discrete Inborn Errors of Metabolism.Metabolites · 2022Review
- Inborn errors of metabolism associated with 3-methylglutaconic aciduria.Clinica chimica acta; international journal of clinical chemistry · 2021Review
- Isomerization ofJIMD reports · 2021Article
- trans-3-Methylglutaconyl CoA isomerization-dependent protein acylation.Biochemical and biophysical research communications · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Over the past 25 years a growing number of distinct syndromes/mutations associated with compromised mitochondrial function have been identified that share a common feature: urinary excretion of 3-methylglutaconic acid (3MGA). In the leucine degradation pathway, carboxylation of 3-methylcrotonyl CoA leads to formation of 3-methylglutaconyl CoA while 3-methylglutaconyl CoA hydratase converts this metabolite to 3-hydroxy-3-methylglutaryl CoA (HMG CoA). In "primary" 3MGA-uria, mutations in the hydratase are directly responsible for the accumulation of 3MGA. On the other hand, in all "secondary" 3MGA-urias, no defect in leucine catabolism exists and the metabolic origin of 3MGA is unknown. Herein, a path to 3MGA from mitochondrial acetyl CoA is proposed. The pathway is initiated when syndrome-associated mutations/DNA deletions result in decreased Krebs cycle flux. When this occurs, acetoacetyl CoA thiolase condenses two acetyl CoA into acetoacetyl CoA plus CoASH. Subsequently, HMG CoA synthase 2 converts acetoacetyl CoA and acetyl CoA to HMG CoA. Under syndrome-specific metabolic conditions, 3-methylglutaconyl CoA hydratase converts HMG CoA into 3-methylglutaconyl CoA in a reverse reaction of the leucine degradation pathway. This metabolite fails to proceed further up the leucine degradation pathway owing to the kinetic properties of 3-methylcrotonyl CoA carboxylase. Instead, hydrolysis of the CoA moiety of 3-methylglutaconyl CoA generates 3MGA, which appears in urine. If experimentally confirmed, this pathway provides an explanation for the occurrence of 3MGA in multiple disorders associated with compromised mitochondrial function.
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Registered trials
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 OpenQuestion graph.