Biochemical and genetic analysis of butyrylcholinesterase (BChE) in a family, due to prolonged neuromuscular blockade after the use of succinylcholine

Abstract

Butyrylcholinesterase (BChE) is a plasma enzyme that catalyzes the hydrolysis of choline esters, including the muscle-relaxant succinylcholine and mivacurium. Patients who present sustained neuromuscular blockade after using succinylcholine usually carry BChE variants with reduced enzyme activity or an acquired BChE deficiency. We report here the molecular basis of the BCHE gene underlying the slow catabolism of succinylcholine in a patient who underwent endoscopic nasal surgery. We measured the enzyme activity of BChE and extracted genomic DNA in order to study the promoter region and all exons of the BCHE gene of the patient, her parents and siblings. PCR products were sequenced and compared with reference sequences from GenBank. We detected that the patient and one of her brothers have two homozygous mutations: nt1615 GCA > ACA (Ala539Thr), responsible for the K variant, and nt209 GAT > GGT (Asp70Gly), which produces the atypical variant A. Her parents and two of her brothers were found to be heterozygous for the AK allele, and another brother is homozygous for the normal allele. Sequence analysis of exon 1 including 5′UTR showed that the proband and her brother are homozygous for –116GG. The AK/AK genotype is considered the most frequent in hereditary hypocholinesterasemia (44%). This work demonstrates the importance of defining the phenotype and genotype of the BCHE gene in patients who are subjected to neuromuscular block by succinylcholine, because of the risk of prolonged neuromuscular paralysis.

Biochemical Markers of In Vivo Hepatotoxicity

“…It is involved in the breakdown of certain drugs, including muscle relaxant drugs called choline esters that are used during general anesthesia. These drugs are given to relax the muscles used for movement (skeletal muscles), including the muscles involved in breathing, and are often employed in emergencies when a breathing tube must be inserted quickly [64]. It also helps protect the body by breaking down certain toxic substances such as pesticides, solanine and poisons that attack the nerves before they reach the nerves.…”

Wide awake under anesthesia: Scoline apnoea update

“…B utirilholinesteraza (BChE) ili pseudoholinesteraza je enzim složene molekularne strukture koji se sintetiše u jetri i odmah oslobađa u plazmu, gde njegov poluživot iznosi 12 dana [1][2][3] . Svojom aktivnošću katalizira hidrolizu holin estara i time inaktiviše mišiće relaksante, kao što su sukcinilholin i mivakurijum [1][2][3][4][5][6] .…”

“…Svojom aktivnošću katalizira hidrolizu holin estara i time inaktiviše mišiće relaksante, kao što su sukcinilholin i mivakurijum [1][2][3][4][5][6] . Sukcinilholin predstavlja lek izbora u slučaju otežane trahealne intubacije, kod pacijenata u riziku od gastroezofagealnog refleksa i kod rapid-sekvens indukcije 1,2,[7][8][9] . Doza sukcinilholina za trahealnu intubaciju iznosi 1 mg/kg, ima brzi nastanak (30-60 s) i krako dejstvo (3-5 min) 10 .…”

“…Kratko dejstvo ovog agensa se povezuje sa njegovom brzom hidrolizom u plazmi, uz pomoć plazma holinesteraze, te je primećeno da kod osoba sa urođenom deficijencijom BChE dolazi do produžene neuromišićne blokade, koja zahteva naknadnu veštačku respiratornu podršku. Nova klinička i genetska istraživanja su upućena na određivanje nivoa enzimske aktivnosti i različitih biohemijskih 1,2,6,7,9 .…”

Butyrylcholinesterase as a biochemical marker

“…Patients with increased sensitivity to succinylcholine and mivacurium have a lowered level of BChE activity in plasma. K variant of BChE (see in chapter devoted to dibucaine number) is responsible for the sensitivity (38). Other forms of familial hypocholinesterasemia can occur as well.…”