Cholinesterase (CHE/BCHE/PCHE)

EC 3.1.1.8

This enzyme is usually referred to as pseudocholinesterase, butyrylcholinesterase, plasma cholinesterase, choline esterase II, or more technically acylcholine acylhydrolase¹. This enzyme is relatively non-specific and catalyzes the hydrolysis of many different choline esters. By contrast, the enzyme more often referred to as cholinesterase, more accurately known as acetylcholinesterase, is more selective for the neurotransmitter acetylcholine, and is found in nerve endings as well as in erythrocytes and other tissues. As the name implies, it is plasma cholinesterase (pseudocholinesterase) that is primarily found in normal plasma or serum. Both types of enzyme catalyze the general reaction shown below, only the specificities differ.

The low specificity of plasma cholinesterase means it can hydrolyze a variety of substrates, and thus can act as a scavenger and general detoxification enzyme, perhaps preventing the action of substances that would otherwise poison acetylcholinesterase, the enzyme critical for neurological function^2,3. Plasma cholinesterase has many diagnostic applications. It is synthesized in the liver and thus can be an accurate reflection of liver function^4,5,6. Whereas other liver enzymes such as ALT and ALP are good indicators of liver tissue damage and are thus typically elevated in serum and plasma, plasma cholinesterase as an indicator of liver function is typically reduced when the liver is not functioning properly.

Many anesthetics act at the neuromuscular junction and can inhibit the action of acetylcholinesterase resulting in temporary muscle paralysis. While this may be desirable during surgery, it is also desirable to end this effect when the surgery is over. Because of the structures of many of these anesthetics, serum cholinesterase is of great importance in inactivating these compounds⁷. Thus people with genetic variants or acquired deficiencies of plasma cholinesterase that result in lower enzymatic activity can have a very difficult time recovering from surgery^8,9,10. It is therefore important to identify individuals with lower serum cholinesterase activities before surgery. One feature of many plasma cholinesterase mutants that display reduced activity is that they also show less susceptibility to certain inhibitors. One such common inhibitor is fluoride, another is dibucaine, and the so-called dibucaine number (the degree to which dibucaine inhibits the enzyme) can be used to predict neuromuscular recovery after surgery^11,12,13. However sometimes inhibitor analysis of plasma cholinesterase does not detect low activity mutants, and more modern methods using genetic analysis have been used in some cases to determine plasma cholinesterase status^14-17.

Because of plasma cholinesterase’s role in hydrolyzing and detoxifying compounds that would otherwise inhibit acetylcholinesterase, resulting in a potentially fatal disruption of the neuromuscular junction, the determination of plasma cholinesterase levels can also be used to detect exposure to pesticides or nerve gases^18,19. Plasma cholinesterase is even being examined as a possible treatment for nerve gas exposure^20,21,22.

REFERENCES

1. 1. Burtis, C.A., Ashwood, E.R. and Bruns, E.R. Tietz Textbook of Clinical Chemistry, 4th Edition, W.B. Saunders Company, 2006.
2. 2. Masson, P., et. al. Structure, Activities and Biomedical Applications of Human Butyrylcholinesterase. Protein and Peptide Letters, 16, 1215-1224, 2009.
3. 3. Masson, P. and Lockridge, O. Butyrylcholinesterase for Protection from Organophosphorus Poisons: Catalytic Complexities and Hysteretic Behavior. Archives of Biochemistry and Biophysics, 494, 107-120, 2010.
4. 4. Evans, D. Pseudocholinesterase Activity in Liver Transplantation. The Lancet, 297, 1040-1044, 1971.
5. 5. Clarke, R.S.J., et. al. Changes in Liver Function After Different Types of Surgery. British Journal of Anaesthesia, 48, 119-128, 1976.
6. 6. Ogunkeye, O. and Roluga, A. Serum Cholinesterase Activity Helps to Distinguish Between Liver Disease and Non-Liver Disease Aberration in Liver Function Tests. Pathophysiology, 13, 91-93, 2006.
7. 7. Davis, L., et. al. Cholinesterase Its Significance in Anaesthetic Practice. Anaesthesia, 52, 244-260, 1997.
8. 8. Viby-Mogensen Correlation of Succinylcholine Duration of Action with Plasma Cholinesterase Activity in Subjects with the Genotypically Normal Enzyme. Anesthesiology, 53, 517-520, 1980.
9. 9. Barta, C., et. al. Analysis of Mutations in the Plasma Cholinesterase Gene of Patients with a History of Prolonged Neuromuscular Block during Anesthesia. Molecular Genetics and Metabolism, 74, 484-488, 2001.
10. 10. Cerf, C., et. al. Screening Patients with Prolonged Neuromuscular Blockade After Succinylcholine and Mivacurium. Anesthesia and Analgesia, 94, 461-466, 2002.
11. 11. Harris, H., et. al. The Pseudocholinesterase Variants. Esterase Levels and Dibucaine Numbers in Families Selected through Suxamethonium Sensitive Individuals. Acta Genet Stat Med, 10, 1-16, 1960.
12. 12. Doutin, D. and Brodeur, J. An Automated Method for Simultaneous Determination of Serum Pseudocholinesterase Activity, Dibucaine Number and Fluoride Number. Clinical Biochemistry, 3, 245-254, 1970.
13. 13. Muensch, H., et. al. Structural Difference at the Active Site of Dibucaine Resistant Variant of Human Plasma Cholinesterase. Am J Hum Genet, 30, 302-307, 1978.
14. 14. Levano, S., et. al. Genotyping the Butyrylcholinesterase in Patients with Prolonged Neuromuscular Block after Succinylcholine. Anesthesiology, 102, 531-535, 2005.
15. 15. Gatke, M.R. Two Novel Mutations in the BCHE Gene in Patients with Prolonged Duration of Action of Mivacurium or Succinylcholine During Anaesthesia. Pharmacogenetics and Genomics, 17, 995-999, 2007.
16. 16. Gatke, M.R., et. al. Better Classification of Butyrylcholinesterase Variants Using Genotype Determination. Annual Meeting Abstracts, American Society of Anesthesiologists, A366, 2008.
17. 17. Landau, R. Pharmacogenetic Influences in Obstetric Anaesthesia. Obstetrics and Gynaecology, 24, 277-287, 2010.
18. 18. Karalliedde, L. Organophosphorus Poisoning and Anaesthesia. Anaesthesia, 54, 1073-1088, 1999.
19. 19. Eddleston, M., et. al. Management of Acute Organophosphorus Pesticide Poisoning. The Lancet, 371, 597-607, 2008.
20. 20. Amitay, M. and Shurki, A. The Structure of G117H Mutant of Butyrylcholinesterase: Nerve Agents Scavenger. Proteins: Structure, Function and Bioinformatics, 77, 370-377, 2009.
21. 21. Chilukuri, N., et. al. Adenovirus-Transduced Human Butyrylcholinesterase in Mouse Blood Functions as a Bioscavenger of Chemical Warfare Nerve Agents. Molecular Pharmacology, 76, 612-617, 2009.
22. 22. Butyrylcholinesterase as a Therapeutic Drug for Protection against Percutaneous VX. Chemico-Biological Interactions, 187, 249-252, 2010.