ReviewJournal of inherited metabolic disease2014
Lipoic acid biosynthesis defects.
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 122 papers.
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Who cites it
122 citing papers in PubMed, 265 citations in OpenAlex.
- Irritable Bowel Disease: Think Malonic and Methylmalonic Aciduria (CMAMMA)!JIMD reports · 2026Article
- Review
- Mitochondrial copper stabilizes lipoylated TCA cycle proteins to sustain metabolism and proliferation.bioRxiv : the preprint server for biology · 2026Article
- Brain-targeted extracellular vesicles for anti-cuproptosis therapy in subarachnoid haemorrhage.Stroke and vascular neurology · 2026Article
- NBR1-Mediated Autophagic Degradation of YTHDF1 CurtailsCancer communications (London, England) · 2026Article
- Targeting multiple genetic defects of mitochondrial diseases with a single bacterial lipoate protein ligase.Science advances · 2025Article
- Lipoyl deglutarylation by ABHD11 regulates mitochondrial and T cell metabolism.Nature chemical biology · 2025Article
- Targeting cuproptosis in liver cancer: Molecular mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2025Review
- Protein lipoylation in cancer: metabolic reprogramming and therapeutic potential.Cell death discovery · 2025Review
- NEDD4L induces mitochondrial dysfunction and neurodegeneration by promoting LIPT2 degradation in Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural basis for catalysis by human lipoyl synthase.Nature communications · 2025Article
- Lipoic acid functions in Paneth cells to prevent human intestinal stem cell aging.Nature communications · 2025Article
- Alpha-Lipoic Acid in Diabetic Peripheral Neuropathy: Addressing the Challenges and Complexities Surrounding a 70-Year-Old Compound.Current issues in molecular biology · 2025Review
- Enhancing Nutraceutical Efficacy: The Role of M.A.T.R.I.S. Technology in Modulating Intestinal Release of Lipoic Acid and L-Carnitine.International journal of molecular sciences · 2025Article
- Copper in cancer: friend or foe? Metabolism, dysregulation, and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- MACAW: a method for semi-automatic detection of errors in genome-scale metabolic models.Genome biology · 2025Article
- Interactions between ferroptosis and tumour development mechanisms: Implications for gynaecological cancer therapy (Review).Oncology reports · 2025Review
- Cuproptosis: Mechanism and Application in Lymphoma.Current cancer drug targets · 2025Review
- Defining the necessity of the lipoic acid synthasemicroPublication biology · 2025Article
- Identification of immune characteristic biomarkers and therapeutic targets in cuproptosis for rheumatoid arthritis by integrated bioinformatics analysis and single-cell RNA sequencing analysis.Frontiers in medicine · 2025Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipoate is a covalently bound cofactor essential for five redox reactions in humans: in four 2-oxoacid dehydrogenases and the glycine cleavage system (GCS). Two enzymes are from the energy metabolism, α-ketoglutarate dehydrogenase and pyruvate dehydrogenase; and three are from the amino acid metabolism, branched-chain ketoacid dehydrogenase, 2-oxoadipate dehydrogenase, and the GCS. All these enzymes consist of multiple subunits and share a similar architecture. Lipoate synthesis in mitochondria involves mitochondrial fatty acid synthesis up to octanoyl-acyl-carrier protein; and three lipoate-specific steps, including octanoic acid transfer to glycine cleavage H protein by lipoyl(octanoyl) transferase 2 (putative) (LIPT2), lipoate synthesis by lipoic acid synthetase (LIAS), and lipoate transfer by lipoyltransferase 1 (LIPT1), which is necessary to lipoylate the E2 subunits of the 2-oxoacid dehydrogenases. The reduced form dihydrolipoate is reactivated by dihydrolipoyl dehydrogenase (DLD). Mutations in LIAS have been identified that result in a variant form of nonketotic hyperglycinemia with early-onset convulsions combined with a defect in mitochondrial energy metabolism with encephalopathy and cardiomyopathy. LIPT1 deficiency spares the GCS, and resulted in a combined 2-oxoacid dehydrogenase deficiency and early death in one patient and in a less severely affected individual with a Leigh-like phenotype. As LIAS is an iron-sulphur-cluster-dependent enzyme, a number of recently identified defects in mitochondrial iron-sulphur cluster synthesis, including NFU1, BOLA3, IBA57, GLRX5 presented with deficiency of LIAS and a LIAS-like phenotype. As in DLD deficiency, a broader clinical spectrum can be anticipated for lipoate synthesis defects depending on which of the affected enzymes is most rate limiting.
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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.