Affinage

BCKDHA

2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial · UniProt P12694

Length
445 aa
Mass
50.5 kDa
Annotated
2026-06-09
100 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCKDHA encodes the E1α subunit of the mitochondrial branched-chain α-ketoacid dehydrogenase (BCKDH) complex, the committed enzymatic step that decarboxylates the ketoacid derivatives of leucine, isoleucine, and valine and channels branched-chain amino acid (BCAA)-derived carbon into the TCA cycle (PMID:40009698, PMID:42136029). Functional holoenzyme assembly requires coordinated coexpression of E1α (BCKDHA) and E1β (BCKDHB): codon-optimized dual-gene delivery of both subunits is necessary and sufficient to reconstitute BCKDH activity in BCKDHA-null cells and to rescue perinatal lethality and MSUD biomarkers in animal models (PMID:40009698). Loss of BCKDHA function causes maple syrup urine disease (MSUD), arising from diverse lesions including nonsense, missense, and splice mutations as well as large structural rearrangements at the 19q13 locus (PMID:10694918, PMID:20431954, PMID:33607070, PMID:36341163). Enzyme activity is governed by the phosphorylation state of the E1α subunit; dephosphorylation activates the complex, and in cancer this activation sustains BCAA catabolism, ATP levels, and radiation resistance, while BCKDHA knockdown increases radiosensitivity (PMID:39672007). BCKDHA transcription is epigenetically controlled through KDM3A binding at its promoter, and its loss reduces mitochondrial TCA-cycle fueling and drives apoptosis in EGFR-mutant tumor cells (PMID:34876693); in melanoma BCKDHA promotes proliferation and invasion by upregulating the lipogenic enzymes FASN and ACLY (PMID:37377173). Beyond peripheral amino acid handling, BCKDHA is required for central nervous system metabolic homeostasis, since its loss elevates brain 2-ketoisocaproate and depletes glutamate/glutamine via reversal of BCAT2 flux (PMID:42136029). The E1α subunit also lies downstream of regulatory inputs from PRSS55 in sperm and is functionally distinct from BCKDK's BCKDHA-independent control of hepatic gluconeogenesis (PMID:39389936, PMID:41444608).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1989 Medium

    Establishing the chromosomal location of BCKDHA was the first step in defining it as a discrete genetic locus for the E1α subunit and a candidate for inherited metabolic disease.

    Evidence In situ hybridization with 3H-labeled cDNA mapping to 19q13.1–q13.2

    PMID:2805821

    Open questions at the time
    • No functional or expression data
    • Did not define gene structure or regulation
  2. 1993 High

    Dissecting the gene's exon structure and promoter revealed how BCKDHA transcription is controlled, including TATA-less initiation and cell-type-specific regulatory elements.

    Evidence Genomic cloning, sequencing, and deletion-reporter luciferase assays in Hep-G2 and CHO cells

    PMID:8463340

    Open questions at the time
    • Trans-acting factors binding the promoter not identified
    • In vivo relevance of cell-type differences unresolved
  3. 1998 Medium

    Linking a specific nonsense mutation to absent enzyme activity established BCKDHA loss-of-function as causative for MSUD.

    Evidence Mutation analysis and enzyme assay in amniocytes from a consanguineous MSUD pedigree (R242X)

    PMID:10694918

    Open questions at the time
    • Single pedigree
    • No biochemical reconstitution of the mutant protein
  4. 2008 Medium

    Characterizing a large intragenic deletion and its breakpoint motif extended the MSUD mutational spectrum to structural rearrangements driven by non-homologous recombination.

    Evidence Long-range PCR and breakpoint sequencing in an MSUD patient (exons 2–4 deletion)

    PMID:19085071

    Open questions at the time
    • Single case
    • Recombination mechanism inferred from motif rather than directly demonstrated
  5. 2009 Medium

    Identifying a founder mutation and recurrent hotspot explained population-level MSUD incidence and the recurrence of certain BCKDHA lesions.

    Evidence Microsatellite haplotyping flanking BCKDHA in Portuguese Gypsy and other populations (c.117delC)

    PMID:19456321

    Open questions at the time
    • No functional characterization of the frameshift allele
    • Hotspot mechanism not molecularly defined
  6. 2010 High

    Demonstrating that an intronic variant creates a cryptic splice site triggering NMD, with residual normal transcript, explained genotype–phenotype correlation for milder variant MSUD.

    Evidence Patient mRNA analysis, emetine rescue, and minigene splicing assay (c.288+9C>T)

    PMID:20431954

    Open questions at the time
    • Quantitative threshold of residual activity for phenotype not defined
    • Single patient context
  7. 2011 Low

    Structural modeling of missense mutations proposed how residue changes near the helical and cofactor/manganese-binding regions impair E1α.

    Evidence Sanger sequencing and PyMOL structural modeling of p.L103P and p.R265P in a Chinese MSUD patient

    PMID:22145486

    Open questions at the time
    • Computational modeling only, no in vitro functional validation
    • Effect on holoenzyme assembly untested
  8. 2021 Medium

    Identifying KDM3A as an epigenetic regulator of BCKDHA established transcriptional control of the gene and linked its expression to mitochondrial energy supply in EGFR-mutant cancer.

    Evidence BIX01294 treatment, BCKDHA knockdown, KDM3A promoter chromatin binding, and metabolic/apoptosis assays in NSCLC cells

    PMID:34876693

    Open questions at the time
    • Single lab and cancer context
    • Direct KDM3A demethylase activity at the locus not biochemically resolved
  9. 2021 Medium

    Mapping an Alu-mediated gross deletion of the entire gene further broadened the structural mutation landscape underlying MSUD.

    Evidence Targeted capture, WGS, CNV PCR, and breakpoint sequencing in a compound heterozygous MSUD patient (exons 1–9 deletion)

    PMID:33607070

    Open questions at the time
    • Single case
    • Recombination mechanism inferred from microhomology
  10. 2022 Medium

    Characterizing a paracentric inversion disrupting intron 1 demonstrated that non-deletional structural rearrangements can also cause classic MSUD.

    Evidence WGS, FISH, and junction-specific sequencing in a compound heterozygous patient

    PMID:36341163

    Open questions at the time
    • Single case
    • Transcriptional consequence of the inversion not directly assayed
  11. 2023 Medium

    Defining a lipogenic axis showed that BCKDHA can act as a pro-tumorigenic gene by upregulating FASN and ACLY, extending its role beyond catabolic housekeeping.

    Evidence Knockdown/overexpression, xenografts, RNA-seq, and rescue experiments in melanoma

    PMID:37377173

    Open questions at the time
    • Mechanism linking BCKDHA to FASN/ACLY induction undefined
    • Single tumor type and lab
  12. 2024 High

    Parallel liver-specific knockouts dissociated BCKDK's control of gluconeogenesis from BCKDHA, showing BCKDK has a BCKDHA-independent role in glucose metabolism.

    Evidence Liver-specific BCKDK and BCKDHA knockout mice, BT2 treatment, CREB–CBP Co-IP, and FOXO1 ubiquitination assays

    PMID:39389936

    Open questions at the time
    • Establishes what BCKDHA does NOT do, not a new BCKDHA function
    • Tissue specificity of the dissociation in non-hepatic contexts unknown
  13. 2024 Medium

    Linking the phosphorylation state of E1α to radiation resistance showed that BCKDH activation sustains ATP and mitigates DNA damage in cancer cells.

    Evidence X-irradiation, BCKDHA phosphorylation analysis, knockdown, and ATP/DSB/mitotic-catastrophe readouts in cancer cells

    PMID:39672007

    Open questions at the time
    • Phosphatase mediating dephosphorylation not identified
    • Mechanism connecting ATP to DSB repair not resolved
  14. 2025 High

    Identifying PRSS55 as a physical partner of the BCKDK–BCKDHA axis placed E1α within a tissue-specific regulatory complex controlling sperm BCAA catabolism and mitochondrial energetics.

    Evidence Prss55 knockout mice, LC-MS/MS proteomics, Co-IP, metabolomics, and mitochondrial function assays in testes/sperm

    PMID:41444608

    Open questions at the time
    • Molecular consequence of PRSS55 binding on BCKDHA activity unresolved
    • Protease substrate relationship not defined
  15. 2025 High

    Demonstrating that coordinated E1α/E1β coexpression reconstitutes holoenzyme activity and rescues disease across models established the obligate two-subunit requirement and a gene therapy strategy.

    Evidence Dual-gene AAV9 delivery, holoenzyme activity assay in BCKDHA-KO HEK293T, Bckdha/Bckdhb KO mice, and a natural bovine MSUD model

    PMID:40009698

    Open questions at the time
    • Long-term durability of rescue not addressed
    • Stoichiometry and assembly intermediates not structurally resolved
  16. 2026 High

    Paired serum-brain metabolomics in knockout mice defined a CNS-specific consequence of BCKDHA loss—BCAT2 flux reversal and glutamate/glutamine depletion—and showed gene therapy normalizes brain neurochemistry.

    Evidence Bckdha−/− mice, paired metabolomics, AAV9 dual-gene rescue, and brain BCKDHA RT-qPCR

    PMID:42136029

    Open questions at the time
    • Cell-type resolution of brain metabolic changes lacking
    • Causal link from neurochemical shifts to neurological phenotype not fully traced

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the phosphorylation/dephosphorylation cycle of E1α is integrated with upstream regulators (PRSS55, KDM3A) and tissue-specific signaling to tune BCKDH activity dynamically remains unresolved.
  • Phosphatase activating BCKDHA in cancer not identified
  • Structural basis of E1α/E1β holoenzyme assembly and cofactor coordination not experimentally solved
  • Mechanism linking BCKDHA to lipogenic enzyme induction undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 2 GO:0016829 lyase activity 2
Localization
GO:0005739 mitochondrion 2
Pathway
R-HSA-1430728 Metabolism 2 R-HSA-1643685 Disease 2
Partners
BCKDHBBCKDKKDM3APRSS55
Complex memberships
branched-chain α-ketoacid dehydrogenase (BCKDH) complex

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 The BCKDHA gene encoding the E1α subunit of branched-chain keto acid dehydrogenase was mapped to human chromosome region 19q13.1–q13.2 by in situ hybridization with 3H-labeled cDNA. Chromosomal in situ hybridization (cytogenetics) Cytogenetics and cell genetics Medium 2805821
1993 The human BCKDHA gene contains 9 exons spanning at least 55 kb; exon 1 is 135 bp with multiple transcription initiation sites at +1, +18, and +22; the promoter lacks a canonical TATA box but contains Sp1, CAAT-like, AP-2, glucocorticoid-responsive element, and cAMP-responsive element sequences. The region for high-level transcription in hepatoma (Hep-G2) cells lies between –320 and –115, with inhibitory elements upstream of –320, while in CHO cells the high-level region extends to –909 to –115, indicating cell-type-specific promoter regulation. Genomic library cloning, sequencing, deletion constructs with luciferase reporter assay in Hep-G2 and CHO cells The Journal of biological chemistry High 8463340
1998 A C-to-T transition in exon 7 of BCKDHA produces a nonsense mutation (R242X) that abolishes branched-chain α-ketoacid dehydrogenase activity, as confirmed in cultured amniocytes with absent enzyme activity from a consanguineous pedigree with MSUD. PCR amplification and mutation analysis of BCKDHA exon 7 in amniocytes with enzyme activity assay Human mutation Medium 10694918
2008 A large deletion of ~13.8 kb in BCKDHA encompassing exons 2–4 (from intron 1 to intron 4) causes MSUD; the deletion junction contains a short CGGG motif present in both introns, supporting non-homologous recombination as the causative mechanism. Long-range PCR and sequencing to characterize deletion breakpoints in a MSUD patient Journal of inherited metabolic disease Medium 19085071
2009 The c.117delC-α (p.R40GfsX23) mutation in BCKDHA is a founder mutation responsible for high MSUD incidence among Portuguese Gypsies, as demonstrated by haplotype analysis with four flanking microsatellite markers; the genomic region around this mutation is a mutational hotspot since it was also found recurrently in distinct population groups. Microsatellite haplotyping and population genetics analysis flanking the BCKDHA gene Annals of human genetics Medium 19456321
2010 The intronic mutation c.288+9C>T in BCKDHA creates a cryptic splice site, causing insertion of a 7-bp fragment from intron 2 into the mRNA with a premature stop codon; this aberrant transcript is subject to nonsense-mediated mRNA decay (NMD), as demonstrated by emetine rescue and minigene splicing assays. A low level of normal mRNA is also produced from this allele, correlating with the milder variant MSUD phenotype observed in the patient (compound heterozygous with the severe p.Gly249Ser allele). Direct mRNA analysis from patient cells, emetine rescue experiment, minigene splicing assay Journal of inherited metabolic disease High 20431954
2011 Two novel missense mutations in BCKDHA — p.L103P (in the helical region) and p.R265P (in the core domain near the cofactor/manganese-binding site) — were identified in a Chinese MSUD patient; structural modeling indicated p.L103P disrupts hydrophobic cores and shortens the helix, while p.R265P affects the cofactor binding site by altering manganese ion coordination. Sanger sequencing of BCKDHA, protein structural modeling with PyMOL Journal of pediatric endocrinology & metabolism : JPEM Low 22145486
2021 BIX01294 (a G9a inhibitor) transcriptionally downregulates BCKDHA expression in EGFR-mutant NSCLC cells through inhibition of KDM3A (a Jumonji histone demethylase) rather than G9a; KDM3A epigenetically regulates BCKDHA expression by binding to the BCKDHA gene promoter. BCKDHA downregulation reduces mitochondrial metabolic function and TCA cycle fueling, leading to decreased cellular energy levels, reduced EGFR protein levels, and apoptosis specifically in EGFR-mutant cells. BIX01294 treatment, BCKDHA knockdown, chromatin binding assay (KDM3A at BCKDHA promoter), mitochondrial metabolic assays, apoptosis assays in NSCLC cells Experimental & molecular medicine Medium 34876693
2021 Alu-element-mediated gross deletion involving exons 1–9 of BCKDHA causes MSUD in a compound heterozygous patient; the deletion breakpoints were mapped within microhomologous sequences in two Alu elements, establishing Alu-mediated recombination as the causative mechanism — the first report of Alu-mediated rearrangement at BCKDHA. Targeted capture sequencing, real-time PCR CNV analysis, whole genome sequencing, long-range PCR, Sanger sequencing to map deletion breakpoints Clinica chimica acta; international journal of clinical chemistry Medium 33607070
2022 A paracentric inversion of chromosome 19 that disrupts intron 1 of BCKDHA causes classic MSUD in compound heterozygosity with a missense variant (p.Ala253Thr); the inversion was identified by whole-genome sequencing and validated by FISH, and the breakpoint junction sequence was characterized, providing mechanistic insight into structural rearrangement at this locus. Whole-genome sequencing, FISH, junction-specific PCR, Sanger sequencing JIMD reports Medium 36341163
2023 BCKDHA promotes melanoma cell proliferation, invasion, migration in vitro and tumor growth in vivo; mechanistically, BCKDHA upregulates the expression of lipogenic enzymes FASN and ATP-citrate lyase (ACLY), which mediate its oncogenic role, as demonstrated by RNA sequencing and functional rescue experiments. In vitro cell biology (knockdown/overexpression), in vivo xenograft model, RNA sequencing, immunohistochemistry, bioinformatics Experimental dermatology Medium 37377173
2024 BCKDK regulates hepatic gluconeogenesis independently of BCKDHA: liver-specific BCKDK knockout inhibits hepatic glucose production and gluconeogenic enzyme expression, whereas liver-specific BCKDHA knockout has no effect on gluconeogenesis. Mechanistically, BT2-mediated BCKDK inhibition attenuates interaction of CREB with CREB-binding protein and promotes FOXO1 ubiquitination and degradation, establishing a BCKDHA-independent pathway for BCKDK in glucose metabolism. Liver-specific knockout mice (BCKDK and BCKDHA), primary hepatocyte experiments, BT2 inhibitor treatment, BCKDK overexpression, co-immunoprecipitation (CREB–CBP interaction), ubiquitination assay for FOXO1 Cell death & disease High 39389936
2024 Dephosphorylation (activation) of BCKDHA promotes BCAA catabolism and renders cancer cells resistant to X-irradiation by maintaining ATP levels and mitigating DNA damage (mitotic catastrophe and residual double-strand breaks). X-irradiation dose-dependently dephosphorylates BCKDHA, suggesting BCKDH complex activation; BCKDHA knockdown increases radiosensitivity. X-irradiation of cancer cells, BCKDHA phosphorylation state analysis, BCKDHA knockdown, measurement of ATP levels, mitotic catastrophe, and residual DSBs Biochemical and biophysical research communications Medium 39672007
2025 PRSS55 (testis-specific serine protease) physically interacts with both BCKDK and BCKDHA in mouse testes and sperm, as validated by LC-MS/MS proteomics and Co-IP; loss of PRSS55 leads to accumulation of BCAAs (valine, leucine, isoleucine) and impaired mitochondrial function/ATP production in sperm, establishing PRSS55 as a regulator of BCAA catabolism upstream of the BCKDK–BCKDHA axis. Prss55 knockout mice, proteomics (LC-MS/MS), metabolomics, Co-IP, immunofluorescence, immunoblotting, mitochondrial function assays (ATP, membrane potential) Cell & bioscience High 41444608
2025 Dual-gene AAV9 vector (rAAV9.hA-BiP-hB) delivering codon-optimized BCKDHA and BCKDHB restores BCKDH holoenzyme activity in BCKDHA-knockout HEK293T cells and rescues perinatal lethality, normalizes growth, and stabilizes MSUD biomarkers in both Bckdha and Bckdhb mouse models and a newborn calf with BCKDHA c.248C>T. Coordinated BCKDHA and BCKDHB coexpression is required for holoenzyme activity, demonstrating that both E1α and E1β subunits are necessary for functional BCKDH complex assembly. AAV9 gene delivery, BCKDH holoenzyme activity assay in HEK293T cells, Bckdha/Bckdhb knockout mouse models, natural bovine MSUD model, biochemical and growth outcome measures Science translational medicine High 40009698
2026 In Bckdha−/− mice, BCKDH deficiency causes a 9-fold elevation of brain 2-ketoisocaproate, cerebral depletion of glutamate and glutamine, and disruption of TCA cycle and ketone body metabolism; these arise from reversal of branched-chain aminotransferase 2 (BCAT2) flux and destabilization of glutamate–2-ketoglutarate mass balance. Systemic AAV9 dual-gene therapy (A-BiP-B encoding BCKDHA and BCKDHB) partially restored cerebral BCKDHA mRNA and brought brain neurochemical endpoints within wild-type range, demonstrating that BCKDHA is required for central nervous system metabolic homeostasis beyond peripheral amino acid control. Bckdha−/− mouse model, paired serum-brain metabolomics, AAV9 gene therapy rescue, RT-qPCR for BCKDHA mRNA in brain Molecular therapy : the journal of the American Society of Gene Therapy High 42136029

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Curcumin attenuates MSU crystal-induced inflammation by inhibiting the degradation of IκBα and blocking mitochondrial damage. Arthritis research & therapy 124 31455356
2017 Berberine, an isoquinoline alkaloid suppresses TXNIP mediated NLRP3 inflammasome activation in MSU crystal stimulated RAW 264.7 macrophages through the upregulation of Nrf2 transcription factor and alleviates MSU crystal induced inflammation in rats. International immunopharmacology 97 28068647
2022 Palmatine Protects Against MSU-Induced Gouty Arthritis via Regulating the NF-κB/NLRP3 and Nrf2 Pathways. Drug design, development and therapy 84 35812134
2020 Celastrol ameliorates Propionibacterium acnes/LPS-induced liver damage and MSU-induced gouty arthritis via inhibiting K63 deubiquitination of NLRP3. Phytomedicine : international journal of phytotherapy and phytopharmacology 69 33130474
1999 A novel reduced flavin mononucleotide-dependent methanesulfonate sulfonatase encoded by the sulfur-regulated msu operon of Pseudomonas aeruginosa. Journal of bacteriology 68 10049377
2021 Tetrahydropalmatine attenuates MSU crystal-induced gouty arthritis by inhibiting ROS-mediated NLRP3 inflammasome activation. International immunopharmacology 52 34482265
2018 Changes of Treg/Th17 Ratio in Spleen of Acute Gouty Arthritis Rat Induced by MSU Crystals. Inflammation 45 30039428
2022 Type II collagen facilitates gouty arthritis by regulating MSU crystallisation and inflammatory cell recruitment. Annals of the rheumatic diseases 42 36109143
2020 A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1β as relevant therapy for gout patients. Theranostics 40 32104502
2018 MicroRNA-302b negatively regulates IL-1β production in response to MSU crystals by targeting IRAK4 and EphA2. Arthritis research & therapy 40 29482609
2015 IL-37 inhibits the production of pro-inflammatory cytokines in MSU crystal-induced inflammatory response. Clinical rheumatology 40 26547220
2020 Anti-inflammatory and anti-gouty-arthritic effect of free Ginsenoside Rb1 and nano Ginsenoside Rb1 against MSU induced gouty arthritis in experimental animals. Chemico-biological interactions 35 33038330
1992 Malignant transformation of human fibroblast cell strain MSU-1.1 by (+-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene. Proceedings of the National Academy of Sciences of the United States of America 35 1549589
2023 MSU crystal deposition contributes to inflammation and immune responses in gout remission. Cell reports 34 37756161
2020 Management of Gout-associated MSU crystals-induced NLRP3 inflammasome activation by procyanidin B2: targeting IL-1β and Cathepsin B in macrophages. Inflammopharmacology 34 33006110
2018 Resveratrol attenuates the MSU crystal-induced inflammatory response through the inhibition of TAK1 activity. International immunopharmacology 29 30537632
2010 Differences in MSU-induced superoxide responses by neutrophils from gout subjects compared to healthy controls and a role for environmental inflammatory cytokines and hyperuricemia in neutrophil function and survival. The Journal of rheumatology 28 20395644
2022 Lipoxin A4 attenuates MSU-crystal-induced NLRP3 inflammasome activation through suppressing Nrf2 thereby increasing TXNRD2. Frontiers in immunology 27 36569930
2021 Curcumin analogue AI-44 alleviates MSU-induced gouty arthritis in mice via inhibiting cathepsin B-mediated NLRP3 inflammasome activation. International immunopharmacology 24 33517224
2021 β-Caryophyllene Ameliorates MSU-Induced Gouty Arthritis and Inflammation Through Inhibiting NLRP3 and NF-κB Signal Pathway: In Silico and In Vivo. Frontiers in pharmacology 24 33967792
2009 Effects of extracts from Paederia scandens (LOUR.) MERRILL (Rubiaceae) on MSU crystal-induced rats gouty arthritis. The American journal of Chinese medicine 23 19655406
2022 Dynamin-Related Protein 1 Is Involved in Mitochondrial Damage, Defective Mitophagy, and NLRP3 Inflammasome Activation Induced by MSU Crystals. Oxidative medicine and cellular longevity 22 36338340
2021 Effects of Gentiopicroside on activation of NLRP3 inflammasome in acute gouty arthritis mice induced by MSU. Journal of natural medicines 21 34586567
2025 Anemoside B4 targets NEK7 to inhibit NLRP3 inflammasome activation and alleviate MSU-induced acute gouty arthritis by modulating the NF-κB signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 19 39939033
2023 Polydatin ameliorates inflammation and oxidative stress associated with MSU-induced gouty arthritis in mice by regulating PPAR-γ and ferritin activation. Life sciences 19 37209866
2022 POP1 inhibits MSU-induced inflammasome activation and ameliorates gout. Frontiers in immunology 19 36225929
2020 Icariin alleviates MSU-induced rat GA models through NF-κB/NALP3 pathway. Cell biochemistry and function 19 33135192
2019 MSU Crystals induce sterile IL-1β secretion via P2X7 receptor activation and HMGB1 release. Biochimica et biophysica acta. General subjects 19 31676289
2018 Fourteen new mutations of BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease (MSUD) in Malaysian population. Molecular genetics and metabolism reports 18 30228974
2000 Malignant transformation of human fibroblast cell strain MSU-1.1 by N-methyl-N-nitrosourea: evidence of elimination of p53 by homologous recombination. Cancer research 18 10945617
2020 1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol (PLAG) Mitigates Monosodium Urate (MSU)-Induced Acute Gouty Inflammation in BALB/c Mice. Frontiers in immunology 17 32395118
2019 Suppression of Syk activation by resveratrol inhibits MSU crystal-induced inflammation in human monocytes. Journal of molecular medicine (Berlin, Germany) 17 30637441
2015 Eleven novel mutations of the BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease in the Chinese population: Report on eight cases. European journal of medical genetics 17 26453840
1993 Characterization of the promoter-regulatory region and structural organization of E1 alpha gene (BCKDHA) of human branched-chain alpha-keto acid dehydrogenase complex. The Journal of biological chemistry 17 8463340
2017 Twenty novel mutations in BCKDHA, BCKDHB and DBT genes in a cohort of 52 Saudi Arabian patients with maple syrup urine disease. Molecular genetics and metabolism reports 16 28417071
2011 Biological hydrogen production by the algal biomass Chlorella vulgaris MSU 01 strain isolated from pond sediment. Bioresource technology 16 20620045
2023 P2X7R Mediates the Synergistic Effect of ATP and MSU Crystals to Induce Acute Gouty Arthritis. Oxidative medicine and cellular longevity 15 36686377
2023 Ozone alleviates MSU-induced acute gout pain via upregulating AMPK/GAS6/MerTK/SOCS3 signaling pathway. Journal of translational medicine 15 38066599
2021 BIX01294 inhibits EGFR signaling in EGFR-mutant lung adenocarcinoma cells through a BCKDHA-mediated reduction in the EGFR level. Experimental & molecular medicine 15 34876693
2019 Alpha2B-Adrenergic Receptor Regulates Neutrophil Recruitment in MSU-Induced Peritoneal Inflammation. Frontiers in immunology 15 30941135
2020 Total saponin of Dioscorea collettii attenuates MSU crystal‑induced inflammation via inhibiting the activation of the NALP3 inflammasome and caspase‑1 in THP‑1 macrophages. Molecular medicine reports 14 32236574
2020 The novel rexinoid MSU-42011 is effective for the treatment of preclinical Kras-driven lung cancer. Scientific reports 14 33335263
2024 Resolution of acute inflammation induced by monosodium urate crystals (MSU) through neutrophil extracellular trap-MSU aggregate-mediated negative signaling. Journal of inflammation (London, England) 13 39605016
2023 Discovery of a selective NLRP3-targeting compound with therapeutic activity in MSU-induced peritonitis and DSS-induced acute intestinal inflammation. Cellular and molecular life sciences : CMLS 13 37498355
2019 IL-33 Ameliorates the Development of MSU-Induced Inflammation Through Expanding MDSCs-Like Cells. Frontiers in endocrinology 13 30863362
2023 Autophagy induced by PP121 alleviates MSU crystal-induced acute gouty arthritis via inhibition of the NLRP3 inflammasome. International immunopharmacology 12 37573689
1989 Localization of the human gene for the El alpha subunit of branched chain keto acid dehydrogenase (BCKDHA) to chromosome 19q13.1----q13.2. Cytogenetics and cell genetics 12 2805821
2021 Targeting Tristetraprolin Expression or Functional Activity Regulates Inflammatory Response Induced by MSU Crystals. Frontiers in immunology 11 34335573
2023 Dimethyl fumarate attenuates MSU-induced gouty arthritis by inhibiting NLRP3 inflammasome activation and oxidative stress. European review for medical and pharmacological sciences 10 36734707
2022 MicroRNA-486-5p suppresses inflammatory response by targeting FOXO1 in MSU-treated macrophages. Autoimmunity 10 36226520
2019 Decreased Expression of CD14 in MSU-Mediated Inflammation May Be Associated with Spontaneous Remission of Acute Gout. Journal of immunology research 10 31312662
2009 Revisiting MSUD in Portuguese Gypsies: evidence for a founder mutation and for a mutational hotspot within the BCKDHA gene. Annals of human genetics 10 19456321
2023 Resveratrol alleviates MSU-induced gouty arthritis in rats through inhibition of HIF-1α- and NLRP3-derived IL-1β secretion in macrophages. Cellular and molecular biology (Noisy-le-Grand, France) 9 37715438
2023 The Mycobacterium tuberculosis MmpL3 inhibitor MSU-43085 is active in a mouse model of infection. Microbiology spectrum 9 38078724
2021 Effects of Stephania hainanensis alkaloids on MSU-induced acute gouty arthritis in mice. BMC complementary medicine and therapies 9 34284768
2021 Total Saponin of Dioscorea collettii Attenuates MSU Crystal-Induced Inflammation by Inhibiting the Activation of the TLR4/NF-κB Signaling Pathway. Evidence-based complementary and alternative medicine : eCAM 9 34721647
2019 MSU Crystals Enhance TDB-Mediated Inflammatory Macrophage IL-1β Secretion. Inflammation 9 30806957
2011 Three Korean patients with maple syrup urine disease: four novel mutations in the BCKDHA gene. Annals of clinical and laboratory science 9 21844576
1998 Dose-dependent transformation of cells of human fibroblast cell strain MSU-1.1 by cobalt-60 gamma radiation and characterization of the transformed cells. Radiation research 9 9806600
2023 Ouratea spectabilis and its Biflavanone Ouratein D Exert Potent Anti-inflammatory Activity in MSU Crystal-induced Gout in Mice. Planta medica 8 36626932
2023 BCKDHA contributes to melanoma progression by promoting the expressions of lipogenic enzymes FASN and ACLY. Experimental dermatology 8 37377173
2023 Maresin1 ameliorates MSU crystal-induced inflammation by upregulating Prdx5 expression. Molecular medicine (Cambridge, Mass.) 8 37996809
2022 The protective effects of S14G-humanin (HNG) against mono-sodium urate (MSU) crystals- induced gouty arthritis. Bioengineered 8 34965184
2021 CD300a contributes to the resolution of articular inflammation triggered by MSU crystals by controlling neutrophil apoptosis. Immunology 8 34002852
2014 Increased level of MSU crystal-bound protein apolipoprotein A-I in acute gouty arthritis. Scandinavian journal of rheumatology 8 25178483
2025 Study on the effect and mechanism of ZeXie decoction in treating MSU-induced acute gouty arthritis model through PI3K-AKT-mTOR signaling pathway. International immunopharmacology 7 39952005
2024 ML335 inhibits TWIK2 channel-mediated potassium efflux and attenuates mitochondrial damage in MSU crystal-induced inflammation. Journal of translational medicine 7 39175013
2024 MSU crystallization promotes fibroblast proliferation and renal fibrosis in diabetic nephropathy via the ROS/SHP2/TGFβ pathway. Scientific reports 7 39215017
2023 Adaptation of Lacticaseibacillus rhamnosus CM MSU 529 to Aerobic Growth: A Proteomic Approach. Microorganisms 7 36838278
2022 MicroRNA-181a regulates Treg functions via TGF-β1/Smad axis in the spleen of mice with acute gouty arthritis induced by MSU crystals. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 7 36477951
2024 DUSP1 Mitigates MSU-Induced Immune Response in Gouty Arthritis Reinforcing Autophagy. Frontiers in bioscience (Landmark edition) 6 38940057
2018 Four novel mutations of the BCKDHA, BCKDHB and DBT genes in Iranian patients with maple syrup urine disease. Journal of pediatric endocrinology & metabolism : JPEM 6 29306928
2015 IL-1βR-dependent priming of antitumor CD4+ T cells and sustained antitumor immunity after peri-tumoral treatment with MSU and mycobacteria. Oncoimmunology 6 26451307
2011 Identification of two novel BCKDHA mutations in a Chinese patient with maple syrup urine disease. Journal of pediatric endocrinology & metabolism : JPEM 6 22145486
2008 Maple syrup urine disease due to a new large deletion at BCKDHA caused by non-homologous recombination. Journal of inherited metabolic disease 6 19085071
2025 BCKDHA-BCKDHB digenic gene therapy restores metabolic homeostasis in two mouse models and a calf with classic maple syrup urine disease. Science translational medicine 5 40009698
2025 Triple-Enzyme Mimetic Manganese Nanozyme with Redox-Adaptive Catalysis for Synergistic MSU Degradation and Inflammation Resolution in Acute Gout. Advanced healthcare materials 5 40567054
2024 BCKDH kinase promotes hepatic gluconeogenesis independent of BCKDHA. Cell death & disease 5 39389936
2021 Minimally Invasive Embedding of Saturated MSU Induces Persistent Gouty Arthritis in Modified Rat Model. BioMed research international 5 34212036
2010 Functional characterization of the novel intronic nucleotide change c.288+9C>T within the BCKDHA gene: understanding a variant presentation of maple syrup urine disease. Journal of inherited metabolic disease 5 20431954
1995 Malignant transformation of human fibroblast strain MSU-1.1 by v-fes requires an additional genetic change. International journal of cancer 5 7558443
2024 The alleviatory effects of koumine on MSU-induced gouty arthritis via the TLR4/NF-κB/NLRP3 pathway. Basic & clinical pharmacology & toxicology 4 38828789
2023 Clec12a inhibits MSU-induced immune activation through lipid raft expulsion. Life science alliance 4 37339805
2009 Prenatal diagnosis of a novel mutation, c.529C>T (p.Q177X), in the BCKDHA gene in a family with maple syrup urine disease. Journal of inherited metabolic disease 4 19240989
2025 A novel zinc ferrite nanoparticle protects against MSU-induced gout arthritis via Nrf2/NF-κB/NLRP3 pathway. Life sciences 3 39983819
2025 IL1A regulates MSU-induced apoptosis and inflammatory response through TLR4/MyD88/NF-κB signaling pathway. International journal of medical sciences 3 40657393
2024 Dephosphorylation of branched-chain α-keto acid dehydrogenase E1α (BCKDHA) promotes branched-chain amino acid catabolism and renders cancer cells resistant to X-rays by mitigating DNA damage. Biochemical and biophysical research communications 3 39672007
2010 The Trichoplusia ni cell line MSU-TnT4 does not harbor a latent nodavirus. In vitro cellular & developmental biology. Animal 3 19911241
1998 A nonsense mutation (R242X) in the branched-chain alpha-keto acid dehydrogenase E1alpha subunit gene (BCKDHA) as a cause of maple syrup urine disease. Mutations in brief no. 160. Online. Human mutation 3 10694918
2024 The integrin CD11b inhibits MSU-induced NLRP3 inflammasome activation in macrophages and protects mice against MSU-induced joint inflammation. Arthritis research & therapy 2 38863059
2023 Highly expressed long non-coding RNA SNHG14 activated MSU-induced inflammatory response in acute gout arthritis through targeting miR-223-3p. International journal of rheumatic diseases 2 37715329
2022 Maple syrup urine disease due to a paracentric inversion of chr 19 that disrupts BCKDHA: A case report. JIMD reports 2 36341163
2021 Identification of the first Alu-mediated gross deletion involving the BCKDHA gene in a compound heterozygous patient with maple syrup urine disease. Clinica chimica acta; international journal of clinical chemistry 2 33607070
2025 AduCPI2 alleviates MSU-induced acute gouty arthritis in mice by inhibiting cathepsin S and the C5a-C5aR1 axis. Frontiers in pharmacology 1 40584622
2021 Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease. Journal of pediatric endocrinology & metabolism : JPEM 1 34883003
2026 Pentagalloyl glucose suppresses MSU crystal-induced gout inflammation and arachidonic acid production in vitro and in vivo. Frontiers in pharmacology 0 42110546
2026 Systemic dual-gene therapy reverses biochemical intoxication in the central metabolic compartment of Bckdha-/- mice. Molecular therapy : the journal of the American Society of Gene Therapy 0 42136029
2025 The RXR Agonist MSU-42011 Reduces Tumor Burden in a Murine Preclinical NF1-Deficient Model. Cancers 0 40563570
2025 Mitochondrial calcium uniporter promotes MSU crystal-induced inflammation through inducing mitochondrial Ca2+ overload and ubiquitination of SIRT5 protein. Arthritis research & therapy 0 40846988
2025 PRSS55 regulates BCAA metabolism and interacts with BCKDK and BCKDHA in mouse testes and sperm. Cell & bioscience 0 41444608

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