Butyrylcholinesterase (BuChE) Protein
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Butyrylcholinesterase (BuChE)</th>
</tr>
<tr> [@tetrameric2006]
<td class="label">Gene</td> [@buche2013]
<td><a href="/genes/bche">BCHE</a></td> [@plasma2013]
</tr> [@buche2016]
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P06276" target="_blank">P06276</a></td>
</tr>
<tr>
<td class="label">PDB Structures</td>
<td><a href="https://www.rcsb.org/structure/1XUU" target="_blank">1XUU</a>, <a href="https://www.rcsb.org/structure/2J4C" target="_blank">2J4C</a>, <a href="https://www.rcsb.org/structure/4W2N" target="_blank">4W2N</a></td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~68 kDa (tetrameric glycoprotein)</td>
</tr>
<tr>
<td class="label">Length</td>
<td>574 amino acids</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma, Liver, Brain ([astrocytes](/entities/astrocytes), microglia)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Cholinesterase family, Serpentine superfamily</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>Pseudocholinesterase, Serum cholinesterase, BuChE, BChE</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/
...Butyrylcholinesterase (BuChE) Protein
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Butyrylcholinesterase (BuChE)</th>
</tr>
<tr> [@tetrameric2006]
<td class="label">Gene</td> [@buche2013]
<td><a href="/genes/bche">BCHE</a></td> [@plasma2013]
</tr> [@buche2016]
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P06276" target="_blank">P06276</a></td>
</tr>
<tr>
<td class="label">PDB Structures</td>
<td><a href="https://www.rcsb.org/structure/1XUU" target="_blank">1XUU</a>, <a href="https://www.rcsb.org/structure/2J4C" target="_blank">2J4C</a>, <a href="https://www.rcsb.org/structure/4W2N" target="_blank">4W2N</a></td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~68 kDa (tetrameric glycoprotein)</td>
</tr>
<tr>
<td class="label">Length</td>
<td>574 amino acids</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma, Liver, Brain ([astrocytes](/entities/astrocytes), microglia)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Cholinesterase family, Serpentine superfamily</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>Pseudocholinesterase, Serum cholinesterase, BuChE, BChE</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/anxiety" style="color:#ef9a9a">Anxiety</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">75 edges</a></td>
</tr>
</table>
Butyrylcholinesterase (BuChE) Protein
Introduction
Butyrylcholinesterase (Buche) Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
Butyrylcholinesterase (BuChE, also known as pseudocholinesterase or serum cholinesterase) is a 574-amino acid glycoprotein enzyme encoded by the BCHE gene [@butyrylcholinesterase2010]. It belongs to the cholinesterase family of enzymes that hydrolyze choline esters, and is distinguished from acetylcholinesterase (AChE) by its substrate preference for butyrylcholine over acetylcholine [@structure1999].
BuChE is primarily synthesized in the liver and circulates in plasma at relatively high concentrations (~5-8 mg/L) [@clinical2003]. However, it is also expressed in the brain, particularly in glial cells, where it plays important roles in cholinergic signaling and has been implicated in neurodegenerative diseases [@role2005].
Structure
Overall Architecture
BuChE is a tetrameric glycoprotein composed of four identical subunits [@tetrameric2006]:
- Each subunit: ~68 kDa
- Total tetramer: ~270 kDa
- Glycosylation: significant N-linked carbohydrates (~24% of mass)
Structural Features
| Feature | Description |
|---------|-------------|
| Catalytic triad | Ser198, His438, Glu325 (cholinesterase signature) |
| Acyl pocket | Determines substrate specificity |
| Peripheral site | Binding site for inhibitors |
| Glycosylation | 9 N-linked glycosylation sites |
| C-terminal | Tetramerization domain |
Active Site
The active site of BuChE contains [@structure1999]:
- Serine at position 198 — nucleophilic attack on ester bonds
- Histidine at position 438 — general base catalysis
- Glutamate at position 325 — orienting histidine
- Acyl pocket — larger than AChE, accommodates butyrylcholine
- Choline binding pocket — recognizes quaternary ammonium
Structural Comparisons
| Feature | BuChE | AChE |
|---------|-------|------|
| Subunit size | ~68 kDa | ~70 kDa |
| Oligomerization | Tetramers | Dimers/tetramers |
| Glycosylation | Higher | Lower |
| Acyl pocket | Large (butyryl) | Small (acetyl) |
| Peripheral site | Present | Present |
Normal Function
Catalytic Activity
BuChE catalyzes the hydrolysis of choline esters [@butyrylcholinesterase2010]:
Acetylcholine + H₂O → Acetic acid + Choline
Butyrylcholine + H₂O → Butyric acid + Choline
Substrate Specificity
- Primary substrate: Butyrylcholine
- Also hydrolyzes: [Acetylcholine](/entities/acetylcholine), propionylcholine, benzoylcholine
- Inhibited by: Organophosphates, carbamates, nerve agents
Physiological Roles
BuChE hydrolyzes several clinically important drugs [@clinical2003]:
- Suxamethonium — muscle relaxant (prolonged effect in BCHE deficiency)
- Cocaine — metabolic clearance
- Heroin — hydrolysis to 6-MAM
- Aspirin — minor pathway
Cholinergic Signaling
In the brain, BuChE contributes to cholinergic transmission <sup><a href="#references">[4]</a> Hydro</sup>:
-lyzes acetylcholine at synapses
- Complements AChE activity
- More important in aging and disease when AChE declines
Other Functions
- Lipid metabolism — potential role in HDL metabolism
- Detoxification — hydrolyzes environmental toxins
- Stress response — cortisol modulation
Role in Disease
Alzheimer's Disease
BuChE is significantly implicated in AD pathogenesis [@role2005][@buche2013]:
Increased Activity in AD
- BuChE activity increases in AD brain (up to 2-fold)
- Activity correlates with disease severity
- Reflects reactive gliosis and neuronal loss
Cholinergic Dysfunction
- Compensatory mechanism for lost AChE
- Higher BuChE/AChE ratio in AD
- Contributes to cholinergic deficiency
Amyloid Interaction
- BuChE colocalizes with amyloid plaques
- May influence [Aβ](/proteins/amyloid-beta) aggregation kinetics
- Modulates Aβ-induced neurotoxicity
Genetic Variants
- BCHE-K variant (D70A) alters drug sensitivity
- Modified AD risk in some populations
- Influences progression and treatment response
Mild Cognitive Impairment
BuChE is a potential biomarker for MCI-to-AD progression [@plasma2013]:
- Elevated activity predicts faster progression
- Combined with AChE improves predictive accuracy
- CSF and plasma measurements under investigation
Parkinson's Disease
- Altered BuChE activity in some PD patients
- Potential biomarker for Lewy body dementia
- May affect cholinergic tone in PD dementia
Therapeutic Targeting
BuChE Inhibitors
BuChE inhibition is being explored for AD treatment [@buche2016]:
| Compound | Type | Status |
|----------|------|--------|
| [Rivastigmine](/entities/rivastigmine) | Carbamate (dual AChE/BuChE) | Approved |
| Iso-OMPA | Selective BuChE inhibitor | Research |
| Cymserine analogs | Selective BuChE inhibitor | Preclinical |
Rationale for Inhibition
- Restore cholinergic transmission
- Reduce Aβ aggregation
- Improve cognitive function
- Neuroprotective effects
See Also
- [Proteins Index](/proteins)
- [Genes Index](/genes)
- [BCHE Gene](/genes/bche)
- [Acetylcholinesterase Protein](/proteins/ache-protein)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Cholinergic Signaling](/mechanisms/cholinergic-signaling-neurodegeneration)
External Links
- UniProt: [https://www.uniprot.org/uniprot/P06276](https://www.uniprot.org/uniprot/P06276)
- PDB: [https://www.rcsb.org/structure/1XUU](https://www.rcsb.org/structure/1XUU)
- AlphaFold: [https://alphafold.ebi.ac.uk/entry/P06276](https://alphafold.ebi.ac.uk/entry/P06276)
- NCBI Protein: [https://www.ncbi.nlm.nih.gov/protein/NP_000046](https://www.ncbi.nlm.nih.gov/protein/NP_000046)
Background
The study of Butyrylcholinesterase (Buche) Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
References
[Unknown, Butyrylcholinesterase: structure, function, and role in Alzheimer's disease. Advances in Experimental Medicine and Biology, 2010 (2010)](https://doi.org/10.1007/978-1-4419-5851-7_5)
[Unknown, Structure of butyrylcholinesterase. Journal of Molecular Biology, 1999 (1999)](https://doi.org/10.1006/jmbi.1999.3291)
[Unknown, Clinical significance of butyrylcholinesterase. Clinica Chimica Acta, 2003 (2003)](https://doi.org/10.1016/S0009-8981(03)
[Unknown, Role of butyrylcholinesterase in Alzheimer's disease. Neurobiology of Aging, 2005 (2005)](https://doi.org/10.1016/j.neurobiolaging.2004.06.009)
[Unknown, Tetrameric architecture of human butyrylcholinesterase. Journal of Biological Chemistry, 2006 (2006)](https://doi.org/10.1074/jbc.M605426200)
[Unknown, BuChE in the progression of Alzheimer's disease. Journal of Alzheimer's Disease, 2013 (2013)](https://doi.org/10.3233/JAD-130119)
[Unknown, Plasma butyrylcholinesterase predicts progression to dementia. Neurology, 2013 (2013)](https://doi.org/10.1212/WNL.0b013e3182825219)
[Unknown, BuChE inhibitors for Alzheimer's disease. Expert Opinion on Therapeutic Targets, 2016 (2016)](https://doi.org/10.1517/14728222.2016.1134483)