DefinitionThis section has been translated automatically.
Acetylcholinesterase (AChE) is a key enzyme that plays an important role in signal transmission through nerve cells. The enzyme is bound to membrane glycolipids and is synthesized into the synaptic cleft.
Here, the catalytic abilities of the enzyme lead to a termination of neurotransmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter acetylcholine to acetate and choline. The acetylcholinesterase works extremely efficiently, has a high number of changes, i.e. the conversion of acetylcholine is extremely fast and is largely diffusion controlled. Naturally, the high speed is necessary to keep the time interval of the excitations transmitted by the neurons as short as possible by immediate degradation of the neurotransmitter.
AChE is mainly found in the nerve-muscle synapse, in the autonomic ganglia, the adrenal medulla and in the cholinergic synapses of the central nervous system. Furthermore, glandular activities of the skin, eyes, digestive tract and bladder, as well as the activity of the heart muscle and smooth and striated muscles are also affected by AChE.
ClassificationThis section has been translated automatically.
There are different isoforms of AChE, which differ in their quaternary structure and solubility behaviour, but not in their enzymatic activity.
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General informationThis section has been translated automatically.
Acetlycholinesterase inhibitors: AChE can be inhibited by organic fluorophosphates, which form very stable covalent phosphoryl enzyme complexes; there is then a constant transmission of stimuli as the acetylcholine is no longer broken down. Many organic phosphate compounds are used as insecticides in agriculture or are so-called nerve poisons.
Acetylcholinesterase inhibitors include the insecticide parathion (E 605), other organophosphoric acid esters such as the chemical warfare agents sarin, tabun and soman. The enzyme acetylcholinesterase thus becomes ineffective and remains in higher concentrations in the synaptic cleft. The resulting increase in parasympathetic tone causes cramps in the gastrointestinal tract. Death is caused by respiratory paralysis. Other AChE inhibitors include strychnine, physostigmine or neostigmine, which also acts as a curare antagonist. It breaks the action of curare, which prevents ACh binding to subsynaptic receptors. Unlike neostigmine, physostigmine is CNS-compliant.
Other inhibitors of AChE include donepezil, rivastigmine, pyridostigmine, tetrahydroaminoacridine and galantamine, all of which are approved for the symptomatic treatment of Alzheimer's disease.
Antagonists of AChE are used as drugs for neurological disorders such as myasthenia gravis or Alzheimer's disease.
Note(s)This section has been translated automatically.
The group of "congenital myasthenic syndromes" are congenital disorders of neuromuscular signal transmission, the cause of which is not an autoimmune process as in myasthenia gravis, but mutations in various genes of the acetylcholine receptor. By changing the receptor kinetics, these mutations lead to a reduced acetylcholinesterase efficiency. The following genes are affected:
- RAPSN (receptor-associated protein of the synapse, 11p11.2-p11.1)
- MuSK (muscle, skeletal, receptor tyrosine kinase, 9q31.3-q32)
- Dok7 (downstream of tyrosine kinase 7).
- SCN4A gene (sodium channel, voltage gated, type IV, alpha subunit; 17q23.1-q25.3)
- The rarer presynaptic forms of congenital myasthenic syndrome are caused by mutations in the gene for choline acetyltransferase (CHAT, 10q11.2).
LiteratureThis section has been translated automatically.
- Alvarez A et al (1997) Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils. J mol biol 272:348-361.
- Bernardi CC et al (2010) Amplification and deletion of the ACHE and BCHE cholinesterase genes in sporadic breast cancer. Cancer Geneet Cytogenet 197:158-65.
- Berson A et al (2008) Changes in readthrough acetylcholinesterase expression modulate amyloid-beta pathology. Brain 131:109-119.
- Birks J (2006) Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev:CD005593.
- Falugi C et al (2012) Early appearance and possible functions of non-neuromuscular cholinesterase activities. Front mole Neurosci 5:54.
- Greenfield S (1996) Non-classical actions of cholinesterases: role in cellular differentiation, tumorigenesis and Alzheimer's disease. Neurochem Int 28:485-490.