Laboratory of Biochemical Neuropharmacology, Kazan Federal University, Kazan, Russian Federation.
Laboratory of Biochemical Neuropharmacology, Kazan Federal University, Kazan, Russian Federation.
Biochem Pharmacol. 2023 Dec;218:115910. doi: 10.1016/j.bcp.2023.115910. Epub 2023 Nov 14.
Butyrylcholinesterase (BChE) is present in plasma and numerous cells and organs. Its physiological function(s) is(are) still unclear. However, this enzyme is of pharmacological and toxicological importance. It displays a broad specificity and is capable of hydrolyzing a wide range of substrates with turnovers differing by several orders of magnitude. Nowaday, these substrates include more than two dozen carboxyl-ester drugs, numerous acetylated prodrugs, and transition state analogues of acetylcholine. In addition, BChE displays a promiscuous hydrolytic activity toward amide bonds of arylacylamides, and slowly hydrolyzes carbamyl- and phosphoryl-esters. Certain pseudo-substrates like carbamates and organophosphates are major drugs of potential medical interest. The existence of a large genetic poly-allelism, affecting the catalytic properties of BChE is at the origin of clinical complications in the use of certain drugs catabolized by BChE. The number of drugs and prodrugs hydrolyzed by BChE is expected to increase in the future. However, very few quantitative data (K, k) are available for most marketed drugs, and except for myorelaxants like succinylcholine and mivacurium, the impact of BChE genetic mutations on catalytic parameters has not been evaluated for most of these drugs.
丁酰胆碱酯酶（BChE）存在于血浆和许多细胞和器官中。其生理功能尚不清楚。然而，这种酶具有药理学和毒理学重要性。它显示出广泛的特异性，能够水解具有相差几个数量级的周转率的广泛范围的底物。如今，这些底物包括二十多种羧酸酯类药物、许多乙酰化前药以及乙酰胆碱的过渡态类似物。此外，BChE 对芳酰基酰胺的酰胺键表现出混杂的水解活性，并缓慢水解氨甲酰基和膦酸酯。某些类似物如氨基甲酸酯和有机磷酸酯是具有潜在医学意义的主要药物。影响 BChE 催化特性的大量遗传多等位基因的存在是某些由 BChE 代谢的药物使用中出现临床并发症的原因。未来预计将有更多的药物和前药被 BChE 水解。然而，对于大多数上市药物，很少有定量数据（K，k）可用，并且除了琥珀酰胆碱和米库氯铵等肌肉松弛剂之外，BChE 遗传突变对大多数这些药物的催化参数的影响尚未得到评估。
