Butyrylcholinesterase and lipid metabolism: Possible dual role in metabolic disorders

Furtado-Alle, Lupe; Tureck, Luciane V.; de Oliveira, Carolina S.; Hortega, João V.M.; Souza, Ricardo L.R.

doi:10.1016/j.cbi.2023.110680

Cited by 3 publications

(2 citation statements)

References 56 publications

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“…Oral DOP is well tolerated and safe for smoking and alcohol cessation [ 51 ]. Cholinesterase plays a key role in lipid metabolism and is also a predisposing factor for metabolic diseases [ 52 ]. Cholinesterase activity is usually higher in diabetic patients than in hyperlipidemia patients [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of co-expressed central genes and transcription factors in acute myocardial infarction and diabetic nephropathy

Li,

Zhao,

Xie

et al. 2024

BMC Med Genomics

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Background Acute myocardial infarction (AMI) and diabetic nephropathy (DN) are common clinical co-morbidities, but they are challenging to manage and have poor prognoses. There is no research on the bioinformatics mechanisms of comorbidity, and this study aims to investigate such mechanisms. Methods We downloaded the AMI data (GSE66360) and DN datasets (GSE30528 and GSE30529) from the Gene Expression Omnibus (GEO) platform. The GSE66360 dataset was divided into two parts: the training set and the validation set, and GSE30529 was used as the training set and GSE30528 as the validation set. After identifying the common differentially expressed genes (DEGs) in AMI and DN in the training set, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and protein–protein interaction (PPI) network construction were performed. A sub-network graph was constructed by MCODE, and 15 hub genes were screened by the Cytohubba plugin. The screened hub genes were validated, and the 15 screened hub genes were subjected to GO, KEGG, Gene MANIA analysis, and transcription factor (TF) prediction. Finally, we performed TF differential analysis, enrichment analysis, and TF and gene regulatory network construction. Results A total of 46 genes (43 up-regulated and 3 down-regulated) were identified for subsequent analysis. GO functional analysis emphasized the presence of genes mainly in the vesicle membrane and secretory granule membrane involved in antigen processing and presentation, lipopeptide binding, NAD + nucleosidase activity, and Toll-like receptor binding. The KEGG pathways analyzed were mainly in the phagosome, neutrophil extracellular trap formation, natural killer cell-mediated cytotoxicity, apoptosis, Fc gamma R-mediated phagocytosis, and Toll-like receptor signaling pathways. Eight co-expressed hub genes were identified and validated, namely TLR2, FCER1G, CD163, CTSS, CLEC4A, IGSF6, NCF2, and MS4A6A. Three transcription factors were identified and validated in AMI, namely NFKB1, HIF1A, and SPI1. Conclusions Our study reveals the common pathogenesis of AMI and DN. These common pathways and hub genes may provide new ideas for further mechanistic studies.

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Section: Discussionmentioning

confidence: 99%

Identification of co-expressed central genes and transcription factors in acute myocardial infarction and diabetic nephropathy

Li,

Zhao,

Xie

et al. 2024

BMC Med Genomics

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“…It is still debated what is the main function of human BChE (hBChE). This enzyme was reported to be involved in lipid metabolism including the ability to hydrolyze the hunger hormone ghrelin (Furtado‐Alle et al, 2023 ). Reversible non‐covalent inhibition of hBChE by small molecules is thought to be a path to treat Alzheimer's disease, each year witnessing hundreds of papers with suggested drug candidates (Jing et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Dynamic interchange between two protonation states is characteristic of active sites of cholinesterases

Zlobin,

Smirnov,

Golovin

2024

Protein Science

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Cholinesterases are well‐known and widely studied enzymes crucial to human health and involved in neurology, Alzheimer's, and lipid metabolism. The protonation pattern of active sites of cholinesterases influences all the chemical processes within, including reaction, covalent inhibition by nerve agents, and reactivation. Despite its significance, our comprehension of the fine structure of cholinesterases remains limited. In this study, we employed enhanced‐sampling quantum‐mechanical/molecular‐mechanical calculations to show that cholinesterases predominantly operate as dynamic mixtures of two protonation states. The proton transfer between two non‐catalytic glutamate residues follows the Grotthuss mechanism facilitated by a mediator water molecule. We show that this uncovered complexity of active sites presents a challenge for classical molecular dynamics simulations and calls for special treatment. The calculated proton transfer barrier of 1.65 kcal/mol initiates a discussion on the potential existence of two coupled low‐barrier hydrogen bonds in the inhibited form of butyrylcholinesterase. These findings expand our understanding of structural features expressed by highly evolved enzymes and guide future advances in cholinesterase‐related protein and drug design studies.

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Improved Affinity: A Customized Fluorescent Probe for the Rapid Detection of Butyrylcholinesterase

Wang,

Chen,

Zhang

et al. 2024

Chemosensors

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This article presents the distinctive butyrylcholinesterase (BChE) fluorescent probe P5, designed via a targeting-site method. This method was proposed to enhance the affinity of the probe for BChE by targeting the peripheral anionic site (PAS) of BChE. By mimicking the natural substrate butyrylcholine, the structure of the probe was optimized by introducing a positive charge. Fluorescent probe P5, selected from a series of designed fluorescent probes P1–P6, exhibited excellent affinity and specificity towards BChE, enabling rapid detection within 5 min with a low detection limit of 16.7 ng/mL. Furthermore, this probe can distinguish between normal cells and Alzheimer’s disease (AD) model cells, and demonstrated good imaging results in a P12 cell AD model. The results of this study indicate that this novel fluorescent probe could serve as a promising tool for the rapid detection of BChE and accurate AD diagnosis.

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Butyrylcholinesterase and lipid metabolism: Possible dual role in metabolic disorders

Cited by 3 publications

References 56 publications

Identification of co-expressed central genes and transcription factors in acute myocardial infarction and diabetic nephropathy

Identification of co-expressed central genes and transcription factors in acute myocardial infarction and diabetic nephropathy

Dynamic interchange between two protonation states is characteristic of active sites of cholinesterases

Improved Affinity: A Customized Fluorescent Probe for the Rapid Detection of Butyrylcholinesterase

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