Butyrylcholinesterase

Butyrylcholinesterase (BCHE, or BuChE), also known as pseudocholinesterase or plasma cholinesterase ) is a non-specific is_associated_with::cholinesterase enzyme that hydrolyses many different choline esters. In humans, it is found primarily in the liver and is encoded by the BCHE is_associated_with::gene.

It is very similar to the neuronal is_associated_with::acetylcholinesterase, which is also known as RBC or erythrocyte cholinesterase. The term "serum cholinesterase" is generally used in reference to a clinical test that reflects levels of both of these enzymes in the blood. Assay of butyrylcholinesterase activity in plasma can be used as a is_associated_with::liver function test as both hypercholinesterasemia and hypocholinesterasemia indicate pathological processes.

is_associated_with::Butyrylcholine is a synthetic compound that does not occur in the body naturally. It is used as a tool to distinguish between acetylcholinesterase and butyrylcholinesterase.

Clinical significance
Pseudocholinesterase deficiency results in delayed metabolism of only a few compounds of clinical significance, including the following: is_associated_with::succinylcholine, is_associated_with::mivacurium, is_associated_with::procaine, is_associated_with::heroin, and is_associated_with::cocaine. Of these, its most clinically important substrate is the depolarizing neuromuscular blocking agent, is_associated_with::succinylcholine, which the pseudocholinesterase enzyme hydrolyzes to succinylmonocholine and then to succinic acid. In individuals with normal plasma levels of normally functioning pseudocholinesterase enzyme, hydrolysis and inactivation of approximately 90-95% of an intravenous dose of succinylcholine occurs before it reaches the neuromuscular junction. The remaining 5-10% of the succinylcholine dose acts as an acetylcholine receptor agonist at the neuromuscular junction, causing prolonged depolarization of the postsynaptic junction of the motor-end plate. This depolarization initially triggers is_associated_with::fasciculation of skeletal muscle. As a result of prolonged depolarization, endogenous acetylcholine released from the presynaptic membrane of the motor neuron does not produce any additional change in membrane potential after binding to its receptor on the myocyte. Flaccid paralysis of skeletal muscles develops within 1 minute. In normal subjects, skeletal muscle function returns to normal approximately 5 minutes after a single bolus injection of succinylcholine as it passively diffuses away from the neuromuscular junction. Pseudocholinesterase deficiency can result in higher levels of intact succinylcholine molecules reaching receptors in the neuromuscular junction, causing the duration of paralytic effect to continue for as long as 8 hours. This condition is recognized clinically when paralysis of the respiratory and other skeletal muscles fails to spontaneously resolve after succinylcholine is administered as an adjunctive paralytic agent during anesthesia procedures. In such cases respiratory assistance is required.

In 2008, an experimental new drug was discovered for the potential treatment of is_associated_with::cocaine abuse and overdose based on the pseudocholiesterase structure. It was shown to remove cocaine from the body 2000 times as fast as the natural form of BChE. Studies in rats have shown that the drug prevented is_associated_with::convulsions and death when administered cocaine overdoses. This enzyme also metabolizes is_associated_with::succinylcholine which accounts for its rapid degradation in the liver and plasma. There may be genetic variability in the kinetics of this enzyme that can lead to prolonged muscle blockade and potentially dangerous respiratory depression that needs to be treated with assisted ventilation.

Mutant alleles at the BCHE locus are responsible for is_associated_with::suxamethonium sensitivity. Homozygous persons sustain prolonged is_associated_with::apnea after administration of the muscle relaxant suxamethonium in connection with surgical is_associated_with::anesthesia. The activity of pseudocholinesterase in the serum is low and its substrate behavior is atypical. In the absence of the relaxant, the is_associated_with::homozygote is at no known disadvantage.

Finally, pseudocholinesterase metabolism of is_associated_with::procaine results in formation of is_associated_with::paraaminobenzoic acid (PABA). If the patient receiving procaine is on sulfonamide antibiotics such as is_associated_with::bactrim the antibiotic effect will be antagonized by providing a new source of PABA to the microbe for subsequent synthesis of is_associated_with::folic acid.

Prophylactic countermeasure against nerve gas
Butyrylcholinesterase is a is_associated_with::prophylactic is_associated_with::countermeasure against is_associated_with::organophosphate is_associated_with::nerve agents. It binds nerve agent in the bloodstream before it can exert effects in the nervous system. Because it is a biological scavenger (and universal target), it is currently the only therapeutic agent effective in providing complete stoichiometric protection against the entire spectrum of organophosphate nerve agents.

Physiological role
It was recently indicated that butyrylcholinesterase could be a physiological ghrelin regulator.

Inhibitors

 * is_associated_with::Cymserine and derivatives
 * is_associated_with::Profenamine
 * is_associated_with::Rivastigmine
 * is_associated_with::Tacrine
 * (+)-ZINC-12613047: IC50 human BChE 13nM, high selectivity over is_associated_with::AChE.