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Function
Choline acetyltransferase (ChAT) catalyzes the synthesis of acetylcholine (ACh) from the precursors choline and acetyl-CoA in cholinergic neurons. The post-translational phosphorylation of ChAT at Ser440 and Thr456 regulate its activity, binding to plasma membrane and interaction with other proteins[1].
Disease
Abnormalities of ChAT in the brain have been demonstrated in schizophrenia and sudden infant death syndrome[2]. Mutations in human ChaT are linked to congenital myasthenic syndrome[3].
Relevance
Greater activity and higher ChAT levels in the hippocampus are associated with better performance on hippocampus-based learning and memory tasks[4]. The concentration of ChaT is reduced in brains of Alzheimer's Disease and ALS patients[5].
Structural highlights
Human ChaT contains 2 domains: substrate-binding and catalytic domain. The active site is a tunnel in which acetyl-CoA is bound at the surface and the choline at the interior pocket.[6]
- ↑ Dobransky T, Rylett RJ. Functional regulation of choline acetyltransferase by phosphorylation. Neurochem Res. 2003 Apr;28(3-4):537-42. PMID:12675142
- ↑ Oda Y. Choline acetyltransferase: the structure, distribution and pathologic changes in the central nervous system. Pathol Int. 1999 Nov;49(11):921-37. PMID:10594838
- ↑ Maselli RA, Chen D, Mo D, Bowe C, Fenton G, Wollmann RL. Choline acetyltransferase mutations in myasthenic syndrome due to deficient acetylcholine resynthesis. Muscle Nerve. 2003 Feb;27(2):180-7. doi: 10.1002/mus.10300. PMID:12548525 doi:https://dx.doi.org/10.1002/mus.10300
- ↑ Hawley WR, Witty CF, Daniel JM, Dohanich GP. Choline acetyltransferase in the hippocampus is associated with learning strategy preference in adult male rats. Behav Brain Res. 2015 Aug 1;289:118-24. doi: 10.1016/j.bbr.2015.04.034. Epub 2015, Apr 27. PMID:25930215 doi:https://dx.doi.org/10.1016/j.bbr.2015.04.034
- ↑ Vijayaraghavan S, Karami A, Aeinehband S, Behbahani H, Grandien A, Nilsson B, Ekdahl KN, Lindblom RP, Piehl F, Darreh-Shori T. Regulated Extracellular Choline Acetyltransferase Activity- The Plausible Missing Link of the Distant Action of Acetylcholine in the Cholinergic Anti-Inflammatory Pathway. PLoS One. 2013 Jun 19;8(6):e65936. doi: 10.1371/journal.pone.0065936. Print 2013. PMID:23840379 doi:https://dx.doi.org/10.1371/journal.pone.0065936
- ↑ Kim AR, Rylett RJ, Shilton BH. Substrate binding and catalytic mechanism of human choline acetyltransferase. Biochemistry. 2006 Dec 12;45(49):14621-31. PMID:17144655 doi:10.1021/bi061536l
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3D Structures of choline O-acetyltransferase
Updated on 07-June-2021
2fy2 – hChaT – human
2fy3 – hChaT + choline
2fy4 – hChaT + CoA
2fy5 – hChaT + CoA derivative
7amd - hChaT + pyridine derivative
1q6x, 1t1u – ChaT – rat
References
