Esterases acyl cholinesterase

Acyl Cholinesterases. Acetylcholinesterase (AChE EC 3.1.1.7 CAS 9000-81-1) is the serine esterase which catalyzes the hydrolysis of acetylcholine and possesses an esteratic site, and which is responsible for unspecific hydrolyses of several substrates. Also, butyrylcholinesterase (EC 3.1.1.8 CAS 9001-08-5) has been sometimes used for asymmetric hydrolysis of esters. Acetylcholinesterase has been used for... 

In contrast to acetylcholinesterase, cholinesterase (acylcholine acyl-hydrolase, butyrylcholinesterase, EC 3.1.1.8) exhibits relatively unspecific esterase activity toward choline esters, with abroad specificity relative to the size of the acyl group. The enzyme is synthesized in the liver and can be found in smooth muscle, adipocytes, and plasma. Its physiological role remains partly obscure, but there is evidence that it is present transiently in the embryonic nervous system, where it is replaced in later stages of development by acetylcholinesterase. It has, therefore, been suggested that cholinesterase functions as an embryonic acetylcholinesterase. 

Other serine hydrolases such as cholinesterases, carboxylesterases, lipases, and fl-lactamases of classes A, C, and D have a hydrolytic mechanism similar to that of serine peptidases [25-27], The catalytic mechanism also involves an acylation and a deacylation step at a serine residue in the active center (see Fig. 3.3). All serine hydrolases have in common that they are inhibited by covalent attachment of diisopropyl phosphorofluoridate (3.2) to the catalytic serine residue. The catalytic site of esterases and lipases has been less extensively investigated than that of serine peptidases, but much evidence has accumulated that they also contain a catalytic triad composed of serine, histidine, and aspartate or glutamate (Table 3.1). 

Thioesters play a paramount biochemical role in the metabolism of fatty acids and lipids. Indeed, fatty acyl-coenzyme A thioesters are pivotal in fatty acid anabolism and catabolism, in protein acylation, and in the synthesis of triacylglycerols, phospholipids and cholesterol esters [145], It is in these reactions that the peculiar reactivity of thioesters is of such significance. Many hydrolases, and mainly mitochondrial thiolester hydrolases (EC 3.1.2), are able to cleave thioesters. In addition, cholinesterases and carboxylesterases show some activity, but this is not a constant property of these enzymes since, for example, carboxylesterases from human monocytes were found to be inactive toward some endogenous thioesters [35] [146], In contrast, allococaine benzoyl thioester was found to be a good substrate of pig liver esterase, human and mouse butyrylcholinesterase, and mouse acetylcholinesterase [147],... 

One group of esterases has an a,p-fold and is prominent in the liver cytosol (Quinn, 1997). Acetylcholinesterase, butyl cholinesterase, and lipases have been used as models for these esterases. Generally esterases also have amidase activity (and vice versa, due to the basic mechanisms). All esterases appear to use a catalytic triad to activate a nucleophile, which is used to form an enzyme-acyl intermediate. The triad consists of a nucleophile, a general base catalyst, and an acidic residue. 

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