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acetylcholinesterase (AcChE)
Function:
- catalyzes hydrolysis of the neurotransmitter acetylcholine in synapses of central & peripheral cholinergic neurons
- occurs in both secreted & membrane-bound forms.
Expression:
- cholinergic neurons in the nucleus basalis express acetylcholinesterase & choline acetyltransferase coordinately
Pharmacology:
- pharamaceutical agents for treatment of Alzheimer's disease & other dementias target inhibition of acetylcholinesterase.
Pathology:
- AcChE activity is predominant over butyrylcholinesterase (BuChE) in normal brain; however, during the course of Alzheimer's disease, the relative proportions of AcChE & BuChE change substantially (reversal).
- the suggestion is made that AcChE may act as a nucleating factor to promote conversion of soluble amyloid peptide into insoluble amyloid fibrils [2]
Genetics: gene locus: 7q22
Related
cholinesterase in serum/plasma
transgenic mouse expressing human amyloid precursor protein (APP) & human acetylcholinesterase
YT blood group locus
General
cholinesterase
oligomerizing protein
Properties
CONFIGURATION:
dimer
SIZE: entity length = 614 aa
MOTIF: signal sequence {1-31}
cysteine residue {C100}
MODIFICATION: cysteine residue {C127}
cysteine residue {C127}
MODIFICATION: cysteine residue {C100}
serine residue {S234}
cysteine residue {C288}
MODIFICATION: cysteine residue {C303}
N-glycosylation site {N296}
cysteine residue {C303}
MODIFICATION: cysteine residue {C288}
active site
glutamate residue {E365}
N-glycosylation site {N381}
cysteine residue {C440}
MODIFICATION: cysteine residue {C560}
histidine residue {H478}
N-glycosylation site {N495}
cysteine residue {C560}
MODIFICATION: cysteine residue {C440}
cysteine residue {C611}
MODIFICATION: cysteine residue {C-INTERCHAIN}
Database Correlations
OMIM correlations
UniProt P22303
Entrez Gene 43
KEGG correlations
ENZYME 3.1.1.7
References
- Role of cholinergic therapy in treatment of Alzheimer's
disease & other dementias, Farlow, M et al, 2001
- Rees T, Hammond PI, Soreq H, Younkin S, Brimijoin S.
Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex.
Neurobiol Aging. Oct;24(6):777-87. 2003
PMID: 12927760
- Mesulam MM, Geula C.
Nucleus basalis (Ch4) and cortical cholinergic innervation in
the human brain: observations based on the distribution of
acetylcholinesterase and choline acetyltransferase.
J Comp Neurol. 1988 Sep 8;275(2):216-40.
PMID: 3220975