Affinage

BCHE

Cholinesterase · UniProt P06276

Length
602 aa
Mass
68.4 kDa
Annotated
2026-06-09
100 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCHE encodes butyrylcholinesterase, a secreted serine hydrolase that circulates in plasma as a tetramer and acts broadly as a choline-ester hydrolase and detoxification enzyme (PMID:1373381, PMID:8622553). Its catalytic machinery depends on a charged Glu441-containing domain and on Ser198 and His438, with intramolecular contacts involving Asp70 and an Ω-loop element shaping substrate positioning; mutations at these and other residues (Val204, Glu441, Gln223) disrupt the catalytic triad and abolish or reduce activity, while substitutions such as Asp70Gly additionally weaken inhibitor and scavenger binding (PMID:1373381, PMID:7489367, PMID:25054547, PMID:33024248). Systematic expression of natural variants resolves residues required for catalysis (e.g., 33, 198, 201, 333) from those required for folding and secretion (e.g., 37, 90, 125, 170), where loss of stabilizing contacts such as the Glu90-Arg42 salt bridge drives intracellular degradation and a silent phenotype (PMID:8554068, PMID:18300943, PMID:17700357). Beyond classical choline esters, BChE hydrolyzes cocaine to inactive products, the orexigenic peptide ghrelin, and a palmitate lipid analog, linking it to drug metabolism, metabolic regulation, and behavior (PMID:8622553, PMID:26915976, PMID:36126749). BChE also carries out enzyme-independent regulatory roles: in hepatocytes it binds PRMT5 and stabilizes it against chaperone-mediated autophagy, sustaining ERK signaling and LDLR-driven cholesterol uptake (PMID:35065166), and in hippocampal and astrocytic systems it modulates the glutamate-glutamine cycle and contextual fear memory without elevating acetylcholine-hydrolyzing activity (PMID:33061920). As a plasma bioscavenger, BChE is targeted and inhibited by carbamates and organophosphates through serine carbamoylation, an activity sensitive to active-site competition by ligands such as L-lactate (PMID:7489367, PMID:10513677, PMID:24900407).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1992 High

    Established which structural elements build BChE's functional catalytic triad and inhibitor-binding sites, defining the residues that make the enzyme catalytically competent.

    Evidence Site-directed mutagenesis of the Glu441 domain and Asp70 in human BCHE expressed in Xenopus oocytes with kinetic and dibucaine-inhibition assays

    PMID:1373381

    Open questions at the time
    • No crystal structure in this study to confirm triad geometry directly
    • Did not address tetramer assembly or secretion
  2. 1990 Medium

    Resolved whether the C5 plasma cholinesterase complex arises from a second BChE gene, showing it is instead a hybrid of BChE with another protein.

    Evidence Southern blot with BCHE exon probes on DNA from CHE2 C5+ individuals

    PMID:2318303

    Open questions at the time
    • Identity of the partner protein not determined here
    • Negative genomic evidence does not define the physical interaction
  3. 1995 Medium

    Showed that the atypical Asp70Gly variant has markedly reduced affinity for carbamate inhibitors and tacrine, establishing Asp70 as critical for inhibitor binding and scavenger function.

    Evidence Enzyme inhibition assays with recombinant atypical BChE and serum from a homozygous carrier across carbamate and acridine inhibitors

    PMID:7489367

    Open questions at the time
    • Single lab
    • Did not test in vivo scavenger efficacy
  4. 1996 High

    Separated catalytic from folding/secretion defects among silent BCHE alleles, mapping residues required for activity versus protein stability.

    Evidence Cell-culture expression of nine mutant constructs with paired enzymatic and immunological readouts

    PMID:8554068

    Open questions at the time
    • Mechanism of folding failure not structurally resolved for each variant
  5. 1996 Medium

    Demonstrated that plasma BChE tetramer metabolizes cocaine to inactive products, defining a detoxification substrate beyond choline esters.

    Evidence Enzyme kinetics with purified human plasma BChE using cocaine as substrate

    PMID:8622553

    Open questions at the time
    • In vitro only
    • Physiological clearance rates in vivo not established here
  6. 2007 Medium

    Extended the variant catalog by linking specific substitutions to activity loss via Ω-loop destabilization or salt-bridge disruption, mechanistically explaining several silent phenotypes.

    Evidence Recombinant expression in HEK293T/CHO cells with Ellman kinetics and molecular dynamics simulations for L88H, E90D, and other variants

    PMID:17700357 PMID:33024248

    Open questions at the time
    • Degradation pathway for unstable variants inferred, not directly traced
    • Single lab
  7. 2008 High

    Distinguished functionally consequential from neutral natural variants, isolating G333C as activity-reducing among several tested.

    Evidence Site-directed mutagenesis and heterologous expression in two cell systems with butyrylthiocholine kinetics

    PMID:18300943

    Open questions at the time
    • Structural basis of G333C effect not resolved
  8. 2014 High

    Provided an atomic-level explanation of how the p.Val204Asp variant disrupts the catalytic triad and impairs tetramer assembly.

    Evidence Patient plasma kinetics, electrophoresis, inhibition studies, and molecular dynamics simulation

    PMID:25054547

    Open questions at the time
    • MD-predicted triad displacement not confirmed by crystallography
  9. 1999 Medium

    Showed that L-lactate competes at the BChE active site and can limit organophosphate inhibition, identifying a small-molecule modulator of scavenger activity.

    Evidence In vitro mixed-inhibition kinetics in human plasma with varying lactate and paraoxon

    PMID:10513677

    Open questions at the time
    • Physiological relevance at lower lactate levels unclear
    • Single lab
  10. 2012 Medium

    Defined the carbamate-transfer mechanism of pseudoirreversible BChE inhibitors and the structural determinants of BChE selectivity.

    Evidence In vitro inhibition kinetics and structure-activity analysis of nitrogen-bridgehead compounds

    PMID:24900407

    Open questions at the time
    • No co-crystal structures
    • Selectivity tested against limited targets
  11. 2010 Medium

    Uncovered a counter-regulatory, signaling-level relationship between BChE and AChE through ERK/PKC pathways, beyond ester hydrolysis.

    Evidence siRNA knockdown in R28 retinal cells with Western blotting of AChE, ERK1/2, PKC, and transcription factors

    PMID:21094673

    Open questions at the time
    • Mechanism connecting BChE loss to AChE upregulation undefined
    • Single lab
  12. 2016 Medium

    Identified ghrelin as an in vivo BChE substrate, linking the enzyme to metabolism and behavior through hormone hydrolysis.

    Evidence Viral BChE overexpression in mice with ghrelin measurement and metabolic/behavioral phenotyping

    PMID:26915976

    Open questions at the time
    • Gain-of-function only
    • Endogenous contribution to ghrelin turnover not quantified
  13. 2016 Low

    Genetically associated the CHE2 C5 complex with RAPH1/lamellipodin, nominating the partner forming the BChE hybrid complex.

    Evidence RAPH1/BCHE haplotype association analysis in CHE2 C5+/C5- individuals with BChE activity measurement

    PMID:27346732

    Open questions at the time
    • Genetic association only, no direct protein-protein interaction or reconstitution
    • Single lab
  14. 2020 Medium

    Established a non-cholinergic CNS role for BChE in regulating the astrocytic glutamate-glutamine cycle and contextual fear memory.

    Evidence AAV-shRNA knockdown in mouse hippocampal CA1 plus astrocyte assays of glutamine synthetase activity and glutamate, with behavioral testing

    PMID:33061920

    Open questions at the time
    • Molecular link between BChE and GS activity not defined
    • Single lab
  15. 2022 High

    Revealed an enzyme-independent scaffolding function: BChE stabilizes PRMT5 against chaperone-mediated autophagy to sustain ERK-LDLR-driven hepatic cholesterol uptake.

    Evidence Reciprocal Co-IP and MS interactome, CMA/HSC70 mechanistic assays, BChE-knockout hepatocytes, LDL uptake assays, and AAV8 hepatocyte-restricted knockdown in mice

    PMID:35065166

    Open questions at the time
    • Structural basis of the BChE-PRMT5 interaction unknown
    • Whether catalytic activity is dispensable not fully dissected
  16. 2022 Medium

    Added lipolytic activity to BChE's substrate repertoire, showing palmitate-ester hydrolysis at the same active site.

    Evidence Hydrolysis of 4-mu palmitate by purified plasma BChE with competitive-inhibition kinetics and molecular docking

    PMID:36126749

    Open questions at the time
    • Physiological lipid substrate not identified
    • In vitro only

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BChE's catalytic versus non-catalytic (scaffolding/signaling) functions are partitioned across tissues, and the structural basis of its protein-protein interactions, remain unresolved.
  • No structural model of BChE-PRMT5 or BChE-lamellipodin complexes
  • Endogenous physiological substrates for ghrelin/lipid activities not established in humans
  • Mechanism linking BChE to astrocytic glutamine synthetase undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0098772 molecular function regulator activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 2 R-HSA-112316 Neuronal System 1
Partners
HSC70PRMT5RAPH1
Complex memberships
C5 cholinesterase complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Site-directed mutagenesis of the conserved Glu441-Ile442-Glu443 domain in BCHE to Gly441-Ile442-Gln443 drastically reduced butyrylthiocholine hydrolysis rate and caused resistance to dibucaine binding, implicating this charged domain as necessary for a functional catalytic triad and for quinoline derivative binding. Additionally, the Asp70Gly ('atypical') substitution reduced hydrolytic activity to 25% of control without altering Km for butyrylthiocholine; normal activity was restored by additional His114 or Tyr561 mutations, revealing intramolecular interactions between N- and C-terminal domains contributing to substrate and inhibitor binding. Site-directed mutagenesis of human BCHE expressed in Xenopus oocytes; kinetic assays with butyrylthiocholine; dibucaine inhibition studies The EMBO journal High 1373381
1995 Recombinant 'atypical' BChE (Asp70Gly variant) showed far lower sensitivity than normal BChE to inhibition by pyridostigmine and other carbamate anti-cholinesterases, and demonstrated approximately 1/200th the affinity for tacrine compared to normal BChE or AChE, establishing that the Asp70 residue is critical for inhibitor binding and scavenger function. Enzyme inhibition assays using recombinant atypical BChE and serum BChE from a homozygous carrier; kinetic analysis with pyridostigmine, carbamates, and tacrine Nature medicine Medium 7489367
1996 Nine silent BCHE alleles with single amino acid substitutions were expressed in cell culture; variants BCHE*33C, BCHE*198G, and BCHE*201T produced normal amounts of immunoreactive but enzymatically inactive BChE protein, while six others caused reduced protein expression. This established that specific residues are required for catalytic activity (positions 33, 198, 201) versus protein folding/secretion (positions 37, 125, 170, 471, 518). Cell culture expression of mutant BCHE constructs; enzymatic activity assays; immunological protein quantification American journal of human genetics High 8554068
1996 Purified human plasma BChE (tetrameric form) metabolizes cocaine to the pharmacologically inactive products ecgonine methylester and benzoic acid, with a Km of 11.9 µM and Vmax of 1.17 µM/min, indicating cocaine is tightly bound to the four active sites of the native tetramer. Enzyme kinetics with purified human plasma BChE using cocaine as substrate Life sciences Medium 8622553
1990 Southern blot analysis of DNA from individuals carrying the CHE2 C5+ plasma cholinesterase variant (also designated CHE2) showed that C5 complex production is not directed by a second butyrylcholinesterase gene, supporting that C5 is a hybrid enzyme formed by association of BChE subunits with a non-cholinesterase protein. Southern blot with probes for all four BCHE exons on DNA from CHE2 C5+ individuals FEBS letters Medium 2318303
2014 The novel BCHE variant p.Val204Asp disrupts the catalytic triad by breaking hydrogen bonding between Gln223 and Glu441, causing Ser198 and His438 to move apart. The mutant enzyme showed pure Michaelian kinetics with elevated Km (265 µM for butyrylthiocholine) and low Vmax, consistent with silent phenotype. Electrophoresis revealed reduced tetrameric enzyme and absence of fast-moving monomeric/dimeric forms in patient plasma. Kinetic analysis of patient plasma BChE; electrophoresis; molecular dynamics simulation; inhibition studies with dibucaine and fluoride PloS one High 25054547
2016 BChE hydrolyzes the peptide hormone ghrelin (the 'hunger hormone') in vivo, and viral gene transfer overexpression of BChE in mice led to lowered circulating ghrelin levels, reduced weight gain on high-fat diets, and reduced aggression, establishing a BChE-ghrelin axis with physiological consequences for metabolism and behavior. Viral gene transfer (overexpression) of BChE in mice; measurement of circulating ghrelin levels; metabolic and behavioral phenotyping Chemico-biological interactions Medium 26915976
2008 Site-directed mutagenesis of four BCHE variants expressed in HEK 293T and CHO cells showed that G333C mutation reduced BChE activity by ~80% relative to wild-type, while K12R, V294M, and R470W variants did not significantly alter enzyme kinetic parameters, establishing specific residue requirements for catalytic activity. Site-directed mutagenesis; heterologous expression in HEK293T and CHO cells; Ellman method for butyrylthiocholine hydrolysis; enzyme kinetics Pharmacogenetics and genomics High 18300943
2007 Expression of BCHE mutant p.Leu88His in cell culture produced BChE with reduced kcat compared to wild-type, while molecular dynamics simulations indicated that this substitution destabilizes the Ω-loop, a structural element implicated in enzyme activity. Three other mutations (p.20delValPheGlyGlyThrValThr, p.Ile140del, p.Arg386Cys) produced no detectable BChE activity (silent phenotype). Recombinant BCHE mutant expression in transfected cells; kinetic analysis; molecular dynamics simulation The pharmacogenomics journal Medium 33024248
2007 Expression of three natural BCHE variants (G75R, E90D, I99M) showed: G75R enzyme has ~45% of wild-type activity; I99M does not differ from wild-type; E90D displays a silent phenotype. The E90D silent phenotype is attributed to disruption of the salt bridge between E90 and R42, likely causing rapid intracellular degradation. Site-directed mutagenesis; expression in HEK293T and CHO cells; Ellman kinetic assay Pharmacogenetics and genomics Medium 17700357
2022 Purified BChE from human plasma hydrolyzed the lipid analog 4-methylumbelliferyl palmitate (4-mu palmitate) at pH 8 with a Km of 34.2 µM, comparable to wheat germ lipase. Competitive inhibition by 4-mu palmitate on butyrylthiocholine hydrolysis (Ki = 448 µM) and molecular docking confirmed that the palmitate substrate binds at the BChE active site, establishing a novel lipolytic activity for BChE. Enzymatic hydrolysis assay with purified BChE; lectin affinity chromatography; inhibition kinetics; molecular docking Biochimie Medium 36126749
2022 BChE interacts with and co-localizes with PRMT5 in hepatocytes. BChE deficiency (knockout) induces PRMT5 degradation via chaperone-mediated autophagy (CMA) by facilitating HSC70 recognition of PRMT5, which reduces ERK signaling and decreases LDLR transcription and LDL uptake. Hepatocyte-restricted BChE silencing in mice reduced plasma cholesterol, establishing a BChE-PRMT5-ERK-LDLR axis in cholesterol metabolism. Co-immunoprecipitation; LC-MS identification of BChE-interacting proteins; BChE knockout hepatocyte cell line; immunoblotting; DiI-LDL uptake assay; AAV8-mediated hepatocyte-restricted BChE knockdown in mice; high-fat diet model Life sciences High 35065166
2010 siRNA knockdown of BChE in R28 retinal cells caused upregulation of AChE and altered ERK1/2 and PKC signaling pathways, including modulation of transcription factors P90RSK1 and c-fos, establishing a counter-regulatory relationship between cholinesterases and their involvement in PKC/ERK signaling cross-talk relevant to cell fate determination. siRNA knockdown; Western blot for AChE, ERK1/2, PKC, P90RSK1, c-fos; electrophysiology; forskolin stimulation Biochimie Medium 21094673
2020 AAV-mediated shRNA knockdown of BChE in mouse hippocampal CA1 region enhanced contextual fear memory and increased dendritic spine density; elevated glutamate levels and glutamine synthetase (GS) enzyme activity were detected in BChE knockdown animals and astrocytes, without elevation of ACh-hydrolyzing activity, establishing a role for BChE in regulating the astrocytic glutamate-glutamine cycle and cognition independently of acetylcholine hydrolysis. AAV-shRNA knockdown in mouse hippocampal CA1; behavioral fear conditioning; dendritic spine density measurement; GS enzymatic activity assay; glutamate level measurement in BChE-knockdown C8D1A astrocytes Frontiers in psychiatry Medium 33061920
2016 The CHE2 locus, which determines the C5 complex variant of BChE, is associated with haplotypes of the RAPH1 gene encoding lamellipodin. RAPH1 haplotypes were associated with CHE2 C5+ phenotype and with differential BChE activity levels, supporting that lamellipodin is the CHE2-encoded BChE-binding protein forming the C5 complex. SNP genotyping of RAPH1 and BCHE in CHE2 C5+ and C5- individuals; haplotype association analysis; BChE activity measurement Annals of human genetics Low 27346732
1999 L-lactate reduces in vitro inhibition of BChE by paraoxon in human plasma when added prior to paraoxon or pre-incubated with paraoxon, acting as a mixed inhibitor of BChE itself at high millimolar concentrations (Ki(EI) = 26 mM, K'I(EIS) = 81 mM), establishing that lactate can compete with organophosphate access to the BChE active site. In vitro BChE activity assay in human plasma; mixed-inhibition kinetics with varying lactate and paraoxon concentrations Journal of applied toxicology : JAT Medium 10513677
2012 Neuroprotective tri- and tetracyclic nitrogen-bridgehead compounds were kinetically characterized as pseudoirreversible BChE inhibitors acting via carbamate transfer to the active site serine of BChE, yielding reversible inhibitor products after carbamoylation; structural elements conferring BChE selectivity and rate of carbamoylation were identified by structure-activity analysis. In vitro enzymatic inhibition kinetics; structure-activity relationship analysis; carbamate transfer mechanism characterization ACS medicinal chemistry letters Medium 24900407

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 A novel WD40 protein, CHE-2, acts cell-autonomously in the formation of C. elegans sensory cilia. Development (Cambridge, England) 99 10518500
1995 Genetic predisposition to adverse consequences of anti-cholinesterases in 'atypical' BCHE carriers. Nature medicine 94 7489367
1991 The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26. Genomics 85 1769657
1996 Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene. American journal of human genetics 83 8554068
2016 Physiological roles for butyrylcholinesterase: A BChE-ghrelin axis. Chemico-biological interactions 79 26915976
2012 Neuroprotective Tri- and Tetracyclic BChE Inhibitors Releasing Reversible Inhibitors upon Carbamate Transfer. ACS medicinal chemistry letters 63 24900407
1999 Further evidence for a synergistic association between APOE epsilon4 and BCHE-K in confirmed Alzheimer's disease. Human genetics 63 10190327
2003 Butyrylcholinesterase (BCHE) genotyping for post-succinylcholine apnea in an Australian population. Clinical chemistry 52 12881446
1997 Amplification of the genes BCHE and SLC2A2 in 40% of squamous cell carcinoma of the lung. Cancer research 49 9187134
1992 Intramolecular relationships in cholinesterases revealed by oocyte expression of site-directed and natural variants of human BCHE. The EMBO journal 49 1373381
2011 GWAS of butyrylcholinesterase activity identifies four novel loci, independent effects within BCHE and secondary associations with metabolic risk factors. Human molecular genetics 46 21862451
1989 Linkage between serum cholinesterase 2 (CHE2) and gamma-crystallin gene cluster (CRYG): assignment to chromosome 2. Clinical genetics 46 2758686
2019 Butyrylcholinesterase Protein Ends in the Pathogenesis of Alzheimer's Disease-Could BCHE Genotyping Be Helpful in Alzheimer's Therapy? Biomolecules 45 31601022
2000 Dipeptidyl carboxypeptidase 1 (DCP1) and butyrylcholinesterase (BCHE) gene interactions with the apolipoprotein E epsilon4 allele as risk factors in Alzheimer's disease and in Parkinson's disease with coexisting Alzheimer pathology. Journal of medical genetics 45 11015454
2005 Four new mutations in the BCHE gene of human butyrylcholinesterase in a Brazilian blood donor sample. Molecular genetics and metabolism 41 15781196
2011 BCHE and CYP2D6 genetic variation in Alzheimer's disease patients treated with cholinesterase inhibitors. European journal of clinical pharmacology 37 21630031
1999 Analysis of association between Alzheimer disease and the K variant of butyrylcholinesterase (BCHE-K). Neuroscience letters 33 10430518
2018 Molecular-docking-guided design and synthesis of new IAA-tacrine hybrids as multifunctional AChE/BChE inhibitors. Bioorganic chemistry 31 30391700
2008 Association of variants of the -116 site of the butyrylcholinesterase BCHE gene to enzyme activity and body mass index. Chemico-biological interactions 30 18550040
2007 Two novel mutations in the BCHE gene in patients with prolonged duration of action of mivacurium or succinylcholine during anaesthesia. Pharmacogenetics and genomics 30 18075469
2010 Amplification and deletion of the ACHE and BCHE cholinesterase genes in sporadic breast cancer. Cancer genetics and cytogenetics 28 20193849
2014 Characterization of a novel BCHE "silent" allele: point mutation (p.Val204Asp) causes loss of activity and prolonged apnea with suxamethonium. PloS one 26 25054547
2013 1914G variant of BCHE gene associated with enzyme activity, obesity and triglyceride levels. Gene 26 24001779
1996 Cocaine and butyrylcholinesterase (BChE): determination of enzymatic parameters. Life sciences 26 8622553
2005 Improved prediction of early-onset coronary artery disease using APOE epsilon4, BChE-K, PPARgamma2 Pro12 and ENOS T-786C in a polygenic model. Clinical biochemistry 25 16298355
1994 Population diversity and distinct haplotype frequencies associated with ACHE and BCHE genes of Israeli Jews from trans-Caucasian Georgia and from Europe. Genomics 25 7806214
2019 Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations. Molecules (Basel, Switzerland) 23 31757047
1990 Two polymorphisms in the non-coding regions of the BCHE gene. Nucleic acids research 23 1978284
2021 Longitudinal evaluation of a novel BChE PET tracer as an early in vivo biomarker in the brain of a mouse model for Alzheimer disease. Theranostics 22 33995675
2008 Five new naturally occurring mutations of the BCHE gene and frequencies of 12 butyrylcholinesterase alleles in a Brazilian population. Pharmacogenetics and genomics 22 18300943
2018 Long non-coding RNA p10247, high expressed in breast cancer (lncRNA-BCHE), is correlated with metastasis. Clinical & experimental metastasis 21 29948648
1990 Evidence for a single butyrylcholinesterase gene in individuals carrying the C5 plasma cholinesterase variant (CHE2). FEBS letters 21 2318303
2020 Rational design of a near-infrared fluorescence probe for highly selective sensing butyrylcholinesterase (BChE) and its bioimaging applications in living cell. Talanta 20 32887168
2017 Evaluating the non-lethal effects of organophosphorous and carbamate insecticides on the yabby (Cherax destructor) using cholinesterase (AChE, BChE), Glutathione S-Transferase and ATPase as biomarkers. Ecotoxicology and environmental safety 19 28554137
2018 Biphasic Alteration of Butyrylcholinesterase (BChE) During Prostate Cancer Development. Translational oncology 18 29966864
2016 New piperidine-hydrazone derivatives: Synthesis, biological evaluations and molecular docking studies as AChE and BChE inhibitors. European journal of medicinal chemistry 18 27592396
2019 Discovery of New Selective Butyrylcholinesterase (BChE) Inhibitors with Anti-Aβ Aggregation Activity: Structure-Based Virtual Screening, Hit Optimization and Biological Evaluation. Molecules (Basel, Switzerland) 17 31311169
2018 K-variant BCHE and pesticide exposure: Gene-environment interactions in a case-control study of Parkinson's disease in Egypt. Scientific reports 17 30410011
2010 Evaluation of candidate genes for cholinesterase activity in farmworkers exposed to organophosphorus pesticides: association of single nucleotide polymorphisms in BCHE. Environmental health perspectives 17 20529763
2022 A far-red/near-infrared fluorescence probe with large Stokes shift for monitoring butyrylcholinesterase (BChE) in living cells and in vivo. Analytica chimica acta 16 36368817
2012 Copy number variation in ACHE/EPHB4 (7q22) and in BCHE/MME (3q26) genes in sporadic breast cancer. Chemico-biological interactions 16 23063927
2011 Obesity and variants of the GHRL (ghrelin) and BCHE (butyrylcholinesterase) genes. Genetics and molecular biology 16 21734817
2012 -116A and K BCHE gene variants associated with obesity and hypertriglyceridemia in adolescents from Southern Brazil. Chemico-biological interactions 15 23000450
2007 Influence of genetic polymorphisms in the apolipoprotein (APOE) and the butyrylcholinesterase (BCHE) gene on stress markers in older adults: a 3-year study. Neurobiology of aging 15 17996334
2022 Novel activity of human BChE: Lipid hydrolysis. Biochimie 14 36126749
2020 Oxidative Stress and Analysis of Selected SNPs of ACHE (rs 2571598), BCHE (rs 3495), CAT (rs 7943316), SIRT1 (rs 10823108), GSTP1 (rs 1695), and Gene GSTM1, GSTT1 in Chronic Organophosphates Exposed Groups from Cameroon and Pakistan. International journal of molecular sciences 14 32899431
2020 Deciphering the Che2 chemosensory pathway and the roles of individual Che2 proteins from Pseudomonas aeruginosa. Molecular microbiology 14 32979856
2010 Counter-regulation of cholinesterases: differential activation of PKC and ERK signaling in retinal cells through BChE knockdown. Biochimie 14 21094673
2005 Possible influence of BCHE locus of butyrylcholinesterase on stature and body mass index. American journal of physical anthropology 14 15386241
2023 Synthesis, computational and experimental pharmacological studies for (thio)ether-triazine 5-HT6R ligands with noticeable action on AChE/BChE and chalcogen-dependent intrinsic activity in search for new class of drugs against Alzheimer's disease. European journal of medicinal chemistry 13 37567058
2022 Hepatocellular BChE as a therapeutic target to ameliorate hypercholesterolemia through PRMT5 selective degradation to restore LDL receptor transcription. Life sciences 13 35065166
2019 Novel Benzene-Based Carbamates for AChE/BChE Inhibition: Synthesis and Ligand/Structure-Oriented SAR Study. International journal of molecular sciences 13 30934674
2013 Acetylcholine-metabolizing butyrylcholinesterase (BCHE) copy number and single nucleotide polymorphisms and their role in attention-deficit/hyperactivity syndrome. Journal of psychiatric research 13 24041656
2024 Discovery of novel bicyclic and tricyclic cyclohepta[b]thiophene derivatives as multipotent AChE and BChE inhibitors, in-Vivo and in-Vitro assays, ADMET and molecular docking simulation. European journal of medicinal chemistry 12 39731791
2023 Influence of the chronic groundwater fluoride consumption on cholinergic enzymes, ACHE and BCHE gene SNPs and pro-inflammatory cytokines: A study with Pakistani population groups. The Science of the total environment 12 37030382
2020 Design, synthesis and biological evaluation of acridone glycosides as selective BChE inhibitors. Carbohydrate research 12 32169593
2015 The rs1803274 polymorphism of the BCHE gene is associated with an increased risk of coronary in-stent restenosis. BMC cardiovascular disorders 11 26497592
2024 Discovery of novel hybrid tryptamine-rivastigmine molecules as potent AChE and BChE inhibitors exhibiting multifunctional properties for the management of Alzheimer's disease. European journal of medicinal chemistry 10 39667052
2011 Biochemical and genetic analysis of butyrylcholinesterase (BChE) in a family, due to prolonged neuromuscular blockade after the use of succinylcholine. Genetics and molecular biology 10 21637541
2024 Novel 6-alkyl-bridged 4-arylalkylpiperazin-1-yl derivatives of azepino[4,3-b]indol-1(2H)-one as potent BChE-selective inhibitors showing protective effects against neurodegenerative insults. European journal of medicinal chemistry 9 38579622
2020 Identification of ovalbumin-derived peptides as multi-target inhibitors of AChE, BChE, and BACE1. Journal of the science of food and agriculture 9 31997357
2020 Acetylcholinesterase inhibition resulting from exposure to inhaled OP can be prevented by pretreatment with BChE in both macaques and minipigs. Neuropharmacology 9 32442543
2019 SAR-mediated Similarity Assessment of the Property Profile for New, Silicon-Based AChE/BChE Inhibitors. International journal of molecular sciences 9 31671776
1999 L-lactate reduces in vitro the inhibition of butyrylcholinesterase (BChE) by paraoxon (E 600). Journal of applied toxicology : JAT 9 10513677
2024 Structure-based design of multitargeting ChEs-MAO B inhibitors based on phenyl ring bioisosteres: AChE/BChE selectivity switch and drug-like characterization. European journal of medicinal chemistry 8 38820854
2020 Genetic Testing for BCHE Variants Identifies Patients at Risk of Prolonged Neuromuscular Blockade in Response to Succinylcholine. Pharmacogenomics and personalized medicine 8 33061533
2018 In-vitro evaluation and in-silico studies applied on newly synthesized amide derivatives of N-phthaloylglycine as Butyrylcholinesterase (BChE) inhibitors. Computational biology and chemistry 8 29653432
2017 Effect of BCHE single nucleotide polymorphisms on lipid metabolism markers in women. Genetics and molecular biology 8 28497838
2016 Novel potent pyridoxine-based inhibitors of AChE and BChE, structural analogs of pyridostigmine, with improved in vivo safety profile. Bioorganic & medicinal chemistry letters 8 27377327
2009 Association of a polymorphism of BCHE with ischemic stroke in Japanese individuals with chronic kidney disease. Molecular medicine reports 8 21475901
1995 Butyrylcholinesterase polymorphisms (BCHE and CHE2 loci) in Brazilian Indian and admixed populations. Human biology 8 8543286
2025 New Mannich-type arylidenerhodanines as potent inhibitors of AChE and BChE: synthesis, biological evaluation, cytotoxicity and molecular modeling. RSC advances 7 41403678
2024 Synthesis of new N-(5,6-methylenedioxybenzothiazole-2-yl)-2-[(substituted)thio/piperazine]acetamide/propanamide derivatives and evaluation of their AChE, BChE, and BACE-1 inhibitory activities. Drug development research 7 38816986
2021 Design, synthesis, crystal structure, in vitro cytotoxicity evaluation, density functional theory calculations and docking studies of 2-(benzamido) benzohydrazide derivatives as potent AChE and BChE inhibitors. RSC advances 7 35424495
2020 Goodyschle A, a new butenolide with significant BchE inhibitory activity from Goodyera schlechtendaliana. Natural product research 7 32208851
2020 Enhanced Contextual Fear Memory and Elevated Astroglial Glutamate Synthase Activity in Hippocampal CA1 BChE shRNA Knockdown Mice. Frontiers in psychiatry 7 33061920
2013 Gestational diabetes mellitus (GDM) decreases butyrylcholinesterase (BChE) activity and changes its relationship with lipids. Genetics and molecular biology 7 24688284
2012 Investigation of Association between Susceptibility to Leprosy and SNPs inside and near the BCHE Gene of Butyrylcholinesterase. Journal of tropical medicine 7 22523498
2024 Allotetraploid nature of a wild potato species, Solanum stoloniferum Schlechtd. et Bché., as revealed by whole-genome sequencing. The Plant journal : for cell and molecular biology 6 39585203
2022 Dysregulation of butyrylcholinesterase, BCHE gene SNP rs1803274, and pro-inflammatory cytokines in occupational workers. Environmental research 6 36592809
2020 Characterization of four BCHE mutations associated with prolonged effect of suxamethonium. The pharmacogenomics journal 6 33024248
2019 Eggplant (Solanum spp) supplemented fruits diet modulated the activities of ectonucleoside triphosphate diphosphohydrolase (ENTPdase), monoamine oxidase (MAO), and cholinesterases (AChE/BChE) in the brain of diabetic Wistar male rats. Journal of food biochemistry 6 31368550
2005 Novel mutations in the BCHE gene in patients with no butyrylcholinesterase activity. Clinica chimica acta; international journal of clinical chemistry 6 15563885
1994 Mutations and impaired expression in the ACHE and BCHE genes: neurological implications. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 6 7999987
2023 Construction of a Label-Free Ratiometric Biosensor Based on Target Recycling Amplification and Hg-ZnSe QDs for Assay of BChE and OPs. Journal of agricultural and food chemistry 5 37554068
2022 Extending the lore of curcumin as dipteran Butyrylcholine esterase (BChE) inhibitor: A holistic molecular interplay assessment. PloS one 5 35617284
2008 Two new mutations of the human BCHE gene (IVS3-14T>C and L574fsX576). Chemico-biological interactions 5 18555211
2006 Molecular basis of succinylcholine sensitivity in a prairie Hutterite kindred and genetic characterization of the region containing the BCHE gene. Molecular genetics and metabolism 5 17166756
1989 Mapping studies of the serum cholinesterase-2 locus (CHE2). Human genetics 5 2777253
2025 Unlocking Therapeutic Potential of Novel Thieno-Oxazepine Hybrids as Multi-Target Inhibitors of AChE/BChE and Evaluation Against Alzheimer's Disease: In Vivo, In Vitro, Histopathological, and Docking Studies. Pharmaceuticals (Basel, Switzerland) 4 40872605
2018 A novel mutation in the BCHE gene and phenotype identified in a child with low butyrylcholinesterase activity: a case report. BMC medical genetics 4 29631548
2013 Functional Analysis and Molecular Docking studies of Medicinal Compounds for AChE and BChE in Alzheimer's Disease and Type 2 Diabetes Mellitus. Aging and disease 4 23936743
2007 Expression of three naturally occurring genetic variants (G75R, E90D, I99M) of the BCHE gene of human butyrylcholinesterase. Pharmacogenetics and genomics 4 17700357
2025 Association of BCHE gene SNP rs1803274 (K-variant) and rs3495 with obesity in Pakistani population group. International journal of obesity (2005) 3 39875593
2024 Pharmacokinetics and fate of free and encapsulated IRD800CW-labelled human BChE intravenously administered in mice. International journal of biological macromolecules 3 39515732
2007 Homozygosity for the K variant of BCHE gene increases the risk for development of neurofibrillary pathology but not amyloid deposits at young ages. Acta neuropathologica 3 17701416
2025 Structural, nonlinear optical, and molecular docking studies of schiff base compounds as multi-target inhibitors of AChE, BChE, and carbonic anhydrases. Scientific reports 2 41053182
2023 New 1,2,3-triazoles and their oxime derivatives: AChE/BChE enzyme inhibitory and DNA binding properties. Journal of biomolecular structure & dynamics 2 38084715
2021 Synthesis and activity of miconazole derivatives as dual BChE/IDO1 inhibitors for the treatment of Alzheimer's disease. Future medicinal chemistry 2 33960203
2016 Association between RAPH1 Gene Haplotypes and CHE2 Locus Phenotypes. Annals of human genetics 2 27346732

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