Cholinesterase

In biochemistry, a cholinesterase or choline esterase is a family of esterases that lyses choline-based esters, several of which serve as neurotransmitters. Thus, it is either of two enzymes that catalyze the hydrolysis of these cholinergic neurotransmitters, such as breaking acetylcholine into choline and acetic acid. These reactions are necessary to allow a cholinergic neuron to return to its resting state after activation. For example, in muscle contraction, acetylcholine at a neuromuscular junction triggers a contraction; but for the muscle to relax afterward, rather than remaining locked in a tense state, the acetylcholine must be broken down by a choline esterase. The main type for that purpose is acetylcholinesterase (also called choline esterase I or erythrocyte cholinesterase); it is found mainly in chemical synapses and red blood cell membranes. The other type is butyrylcholinesterase (also called choline esterase II or plasma cholinesterase); it is found mainly in the blood plasma.AcetylcholineCholineAcetic acidButyrylcholine In biochemistry, a cholinesterase or choline esterase is a family of esterases that lyses choline-based esters, several of which serve as neurotransmitters. Thus, it is either of two enzymes that catalyze the hydrolysis of these cholinergic neurotransmitters, such as breaking acetylcholine into choline and acetic acid. These reactions are necessary to allow a cholinergic neuron to return to its resting state after activation. For example, in muscle contraction, acetylcholine at a neuromuscular junction triggers a contraction; but for the muscle to relax afterward, rather than remaining locked in a tense state, the acetylcholine must be broken down by a choline esterase. The main type for that purpose is acetylcholinesterase (also called choline esterase I or erythrocyte cholinesterase); it is found mainly in chemical synapses and red blood cell membranes. The other type is butyrylcholinesterase (also called choline esterase II or plasma cholinesterase); it is found mainly in the blood plasma. The two types of cholinesterase are acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE). The difference between the two types has to do with their respective preferences for substrates: the former hydrolyses acetylcholine more quickly; the latter hydrolyses butyrylcholine more quickly. The term cholinesterase is sometimes used to refer specifically to butyrylcholinesterase, but this usage produces the oddity that cholinesterase and false cholinesterase (pseudocholinesterase) under that scheme mean the same thing (confusingly), and acetylcholinesterase is then called true cholinesterase in contrast, producing the second oddity that cholinesterase and true cholinesterase then do not mean the same thing. But such usage is now outdated; the current, unambiguous HGNC names and symbols are acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE). Acetylcholinesterase (EC 3.1.1.7) (ACHE), also known as AChE, choline esterase I, RBC cholinesterase, or erythrocyte cholinesterase, true cholinesterase, choline esterase I, or (most formally) acetylcholine acetylhydrolase, is found primarily in the blood on red blood cell membranes, in neuromuscular junctions, and in other neural synapses. Acetylcholinesterase exists in multiple molecular forms. In the mammalian brain the majority of AChE occurs as a tetrameric, G4 form (10) with much smaller amounts of a monomeric G1 (4S) form. Butyrylcholinesterase (EC 3.1.1.8) (BCHE), also known as cholinesterase, choline esterase II, BChE, BuChE, pseudocholinesterase (PCE), plasma cholinesterase (PChE), serum cholinesterase (SChE), butylcholinesterase, or (most formally) acylcholine acylhydrolase, is produced in the liver and found primarily in blood plasma. The butyl and butyryl syllables both refer to butane with one of its terminal methyl groups substituted. The half-life of BCHE is approximately 10 to 14 days. BCHE levels may be reduced in patients with advanced liver disease. The decrease must be greater than 75% before significant prolongation of neuromuscular blockade occurs with succinylcholine. In 1968, Walo Leuzinger et al. successfully purified and crystallized acetylcholinesterase from electric eels at Columbia University, NY. The 3D structure of acetylcholinesterase was first determined in 1991 by Joel Sussman et al. using protein from the Pacific electric ray. Clinically useful quantities of butyrylcholinesterase were synthesized in 2007 by PharmAthene, through the use of genetically modified goats.