Enzymology of cholinesterase and its relevance to peri-operative medicine
Choline is an important nutrient and the main source of which includes diary products such as eggs, meat and milk. Humans can also produce endogenous choline within the liver. (Corbin & Zeisel 2012). Choline has a role in many physiological processes including both lipid transport, cell signalling and neurotransmission (Leermakers et al., 2015). There is increasing evidence linking choline deficiency with disease pathology such as non-alcoholic fatty liver disease (Fischer et al., 2007), growth retardation (Semba et al., 2016), and pathophysiology of neural tube defects (Shaw et al., 2004).
Choline combines with acetic acid to form acetylcholine, a pivotal neurotransmitter within the parasympathetic nervous systemcholine and esters combine to form cholinesters, which have widespread biological activity
Cholinesterases are the enzymes which metabolise cholinesters .They differ in substrate, and distribution throughout tissues. Acetylcholinesterase break down acetycholine (Korabecny & Soukup 2021), important in neurotransmission. pseudocholinesterase (also known as butyrylcholinesterase) (Korabecny & Soukup 2021).
can be distinguished chemically from acetylcholinesterase by its ability to metabolise the synthestic compound butyrylcholine (Silver 1974). Within the human body, both acetycholinesterases and pseudocholinesterase are largely found within the nervous system (Benner et al., 2021). Acetylcholineterase is also found in excitable tissues such as muscles and most RBCs and placenta.
Profile of pseudocholinesterase enzyme
Pseudocholinesterase is responsible for the breakdown succinylcholine into choline and succinic acid (Whittaker & Wijesundera 1951). pseudocholinesterase is synthesised within the liver, and has been proposed as a marker of liver function and may be an independent prognostic marker in pancreatic cancer patients (Klocker et al., 2020). Any condition which affects liver function, such as pregnancy, may reduce pseudocholinesterase levels.mez-Cantarino et al., 2020) Maiorana & Roach 2003).
Pseudocholinesterase deficiency and its relevance to anaesthesia
Pseudocholinesterase deficiency can be either congenital or acquired. and results in the affected person may be unable to break down succinylcholine, mivacurium and other ester-linked muscle relaxants (Robles et al., 2018), with important implications for anaesthetic and its practise leading to a potential prolonged neuromuscular blockade. It is also important to recognise other conditions or drugs which could affect enzyme activity.
Genetics of PChE deficiency
Congenital pseudocholinesetrase deficiency is an austomal recessive trait. The most common genetic variant of the pseudocholinesterase gene or butyrylcholinesterase gene K variant (p.A539T) (Jasiecki et al., 2019), however there are . numerous variants . The most clinically relevant include dibucaine-resistant or atypical, fluoride-resistant, silent variant and the K-variant (Rico-Mora et al., 2018).
The local anaesthetic dibucaine acts as an inhibitor (Lehmann & Liddell 1969). In pharmacology the dibucaine number is often referred to as the percentage inhibition of pseudocholinesterase enzyme. Commonly, a normal dibucaine number within normal individuals is 80% or above. While, heterozygotes have 40%-60% and less than 20% for homozygotes.
Disease conditions and drugs which affect plasma cholinesterase
Before considering the use of anaesthetic agents such as mivacurium, suxamethonium and ester-linked local anaesthetics a detailed anaesethetic history must be taken which should include a family historyThere are certain conditions which can cause raised plasma cholinesterase, includingobesity, fatty liver disease and thyrotoxicosis. A comprehensive list of both physiological and pathological conditions which increase plasma cholinesterase can be recalled by using the acronym CHOLINESTERASE (table 1).
List-1 Physiological and pathological conditions which increase plasma “CHOLINESTERASE”
C Chorea and Concusion
H Hypertension and Hyperlipidaemia
O Obesity
L Liver e.g. fatty liver
I Intestinal e.g. exudative enteropathy
N Nephrotic syndrome
E Endocrine e.g. thyrotoxicosis
S Sex e.g. male
T Tetanus
E Endocrine e.g. diabetes
R Reticulosis
A Alcoholics
S Schizophrenia and anxiety
E Ethnicity?
List-2 Physiological and pathological conditions which decrease plasma “CHOLINESTERASE” <