| Butyrylcholinesterase (BuChE) | |
|---|---|
| Gene | BCHE |
| UniProt | P06276 |
| PDB Structures | 1XUU, 2J4C, 4W2N |
| Molecular Weight | ~68 kDa (tetrameric glycoprotein) |
| Length | 574 amino acids |
| Subcellular Localization | Plasma, Liver, Brain (astrocytes, microglia) |
| Protein Family | Cholinesterase family, Serpentine superfamily |
| Aliases | Pseudocholinesterase, Serum cholinesterase, BuChE, BChE |
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.
Butyrylcholinesterase (BuChE, also known as pseudocholinesterase or serum cholinesterase) is a 574-amino acid glycoprotein enzyme encoded by the BCHE gene [1]. 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 [2].
BuChE is primarily synthesized in the liver and circulates in plasma at relatively high concentrations (~5-8 mg/L) [3]. 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 [4].
BuChE is a tetrameric glycoprotein composed of four identical subunits [5]:
| 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 |
The active site of BuChE contains [2]:
| 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 |
BuChE catalyzes the hydrolysis of choline esters [1]:
Acetylcholine + H₂O → Acetic acid + Choline
Butyrylcholine + H₂O → Butyric acid + Choline
BuChE hydrolyzes several clinically important drugs [3]:
In the brain, BuChE contributes to cholinergic transmission [4] Hydro:
-lyzes acetylcholine at synapses
BuChE is significantly implicated in AD pathogenesis [4][6]:
BuChE is a potential biomarker for MCI-to-AD progression [7]:
BuChE inhibition is being explored for AD treatment [8]:
| Compound | Type | Status |
|---|---|---|
| Rivastigmine | Carbamate (dual AChE/BuChE) | Approved |
| Iso-OMPA | Selective BuChE inhibitor | Research |
| Cymserine analogs | Selective BuChE inhibitor | Preclinical |
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.