ArticleThe Biochemical journal2019
The synthesis of branched-chain fatty acids is limited by enzymatic decarboxylation of ethyl- and methylmalonyl-CoA.
Article in The Biochemical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- Research Progress on Muttony Flavor Regulation and the Establishment of Its Digital Intelligent Evaluation System From a Global Perspective.Comprehensive reviews in food science and food safety · 2026Review
- Integrated Transcriptomic and Proteomic Analysis Associated with Knockdown and Overexpression Studies Revealed ECHDC1 as a Regulator of Intramuscular Fat Deposition in Cattle.Animals : an open access journal from MDPI · 2025Article
- Intermittent Cold Exposure Induces Distinct Proteomic Signatures in White Adipose Tissue of Mice.International journal of molecular sciences · 2025Article
- The enzyme kinetics of branched-chain fatty acid synthesis of metazoan fatty acid synthase.Protein science : a publication of the Protein Society · 2025Article
- Immuno-metabolic stress responses control longevity from mitochondrial translation inhibition in C. elegans.Nature communications · 2025Article
- CLYBL averts vitamin BNature chemical biology · 2025Article
- The emerging role of dysregulated propionate metabolism and methylmalonic acid in metabolic disease, aging, and cancer.Cell metabolism · 2025Review
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- Article
- The N-glycosylation defect in Lec5 and Lec9 CHO cells is caused by absence of the DHRSX gene.bioRxiv : the preprint server for biology · 2024Article
- Mining cholesterol genes from thousands of mouse livers identifies aldolase C as a regulator of cholesterol biosynthesis.Journal of lipid research · 2024Article
- Methylmalonic acid in aging and disease.Trends in endocrinology and metabolism: TEM · 2024Review
- A fatty acid anabolic pathway in specialized-cells sustains a remote signal that controls egg activation in Drosophila.PLoS genetics · 2024Article
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- Branched-Long-Chain Monomethyl Fatty Acids: Are They Hidden Gems?Journal of agricultural and food chemistry · 2023Review
- Insights into energy balance dysregulation from a mouse model of methylmalonic aciduria.Human molecular genetics · 2023Article
- Comparison and analysis on sheep meat quality and flavor under pasture-based fattening contrast to intensive pasture-based feeding system.Animal bioscience · 2022Article
- Effects ofFrontiers in microbiology · 2022Article
- Approaches for completing metabolic networks through metabolite damage and repair discovery.Current opinion in systems biology · 2021Review
- Variants in the ethylmalonyl-CoA decarboxylase (ECHDC1) gene: a novel player in ethylmalonic aciduria?Journal of inherited metabolic disease · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most fatty acids (FAs) are straight chains and are synthesized by fatty acid synthase (FASN) using acetyl-CoA and malonyl-CoA units. Yet, FASN is known to be promiscuous as it may use methylmalonyl-CoA instead of malonyl-CoA and thereby introduce methyl-branches. We have recently found that the cytosolic enzyme ECHDC1 degrades ethylmalonyl-CoA and methylmalonyl-CoA, which presumably result from promiscuous reactions catalyzed by acetyl-CoA carboxylase on butyryl- and propionyl-CoA. Here, we tested the hypothesis that ECHDC1 is a metabolite repair enzyme that serves to prevent the formation of methyl- or ethyl-branched FAs by FASN. Using the purified enzyme, we found that FASN can incorporate not only methylmalonyl-CoA but also ethylmalonyl-CoA, producing methyl- or ethyl-branched FAs. Using a combination of gas-chromatography and liquid chromatography coupled to mass spectrometry, we observed that inactivation of ECHDC1 in adipocytes led to an increase in several methyl-branched FAs (present in different lipid classes), while its overexpression reduced them below wild-type levels. In contrast, the formation of ethyl-branched FAs was observed almost exclusively in ECHDC1 knockout cells, indicating that ECHDC1 and the low activity of FASN toward ethylmalonyl-CoA efficiently prevent their formation. We conclude that ECHDC1 performs a typical metabolite repair function by destroying methyl- and ethylmalonyl-CoA. This reduces the formation of methyl-branched FAs and prevents the formation of ethyl-branched FAs by FASN. The identification of ECHDC1 as a key modulator of the abundance of methyl-branched FAs opens the way to investigate their function.
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