A Method for the Detection of Atypical Forms of Human Serum Cholinesterase. Determination of Dibucaine Numbers*

Kalow, W.; Genest, K.

doi:10.1097/00132586-197312000-00059

Cited by 25 publications

(34 citation statements)

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“…Dibucaine numbers were determined according to the method of Kalow and Genest (1957) and fluoride numbers by the method of Harris and Whittaker (1961), both using benzoyl choline as substrate. Scoline hydrolysis rates were measured by the method of Fishtal et al (1972).…”

Section: Methodsmentioning

confidence: 99%

“…The observations of Kalow and Genest (1957) that this protein could be differentiated from the normal on the basis of a simple biochemical test represented a considerable advance in the laboratory detection of sensitive individuals. These workers showed that the abnormal enzyme was resistant to inhibition by the local anaesthetic agent dibucaine and devised the concept of the dibucaine number (DN), which was defined as the percentage inhibition of the enzyme by 10-5M dibucaine.…”

mentioning

confidence: 99%

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Evidence for mutation being the source of the abnormal gene for plasma cholinesterase

Evans

Magill

1974

Journal of Medical Genetics

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Evidence for mutation being the source of the abnormal gene for plasma cholinesterase

Evans

Magill

1974

Journal of Medical Genetics

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“…The genetic variation of BChE deficiency was described by Kalow and Genest in 1957 and is said to be a cornerstone in pharmacogenetics/pharmacogenomics [4]. The human BCHE gene is located on chromosome 3q26.1 , contains 3 coding exons, and spans approximately 64 kb.…”

Section: Introductionmentioning

confidence: 99%

Characterization of a Novel BCHE “Silent” Allele: Point Mutation (p.Val204Asp) Causes Loss of Activity and Prolonged Apnea with Suxamethonium

et al. 2014

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Butyrylcholinesterase deficiency is characterized by prolonged apnea after the use of muscle relaxants (suxamethonium or mivacurium) in patients who have mutations in the BCHE gene. Here, we report a case of prolonged neuromuscular block after administration of suxamethonium leading to the discovery of a novel BCHE variant (c.695T>A, p.Val204Asp). Inhibition studies, kinetic analysis and molecular dynamics were undertaken to understand how this mutation disrupts the catalytic triad and determines a “silent” phenotype. Low activity of patient plasma butyrylcholinesterase with butyrylthiocholine (BTC) and benzoylcholine, and values of dibucaine and fluoride numbers fit with heterozygous atypical silent genotype. Electrophoretic analysis of plasma BChE of the proband and his mother showed that patient has a reduced amount of tetrameric enzyme in plasma and that minor fast-moving BChE components: monomer, dimer, and monomer-albumin conjugate are missing. Kinetic analysis showed that the p.Val204Asp/p.Asp70Gly-p.Ala539Thr BChE displays a pure Michaelian behavior with BTC as the substrate. Both catalytic parameters Km = 265 µM for BTC, two times higher than that of the atypical enzyme, and a low Vmax are consistent with the absence of activity against suxamethonium. Molecular dynamic (MD) simulations showed that the overall effect of the mutation p.Val204Asp is disruption of hydrogen bonding between Gln223 and Glu441, leading Ser198 and His438 to move away from each other with subsequent disruption of the catalytic triad functionality regardless of the type of substrate. MD also showed that the enzyme volume is increased, suggesting a pre-denaturation state. This fits with the reduced concentration of p.Ala204Asp/p.Asp70Gly-p.Ala539Thr tetrameric enzyme in the plasma and non-detectable fast moving-bands on electrophoresis gels.

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“…The serum cholinesterase dibucaine numbers (DN) of the patient and the other members of the family were determined according to the method described by Kalow and Genest (1957). All the members of the family were also examined for the presence of distichiasis.…”

mentioning

confidence: 99%

Atypical serum cholinesterase in a family with congenital distichiasis.

Shammas¹,

Tabbara²,

Kaloustian³

1976

Journal of Medical Genetics

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A Method for the Detection of Atypical Forms of Human Serum Cholinesterase. Determination of Dibucaine Numbers*

Cited by 25 publications

References 0 publications

Evidence for mutation being the source of the abnormal gene for plasma cholinesterase

Evidence for mutation being the source of the abnormal gene for plasma cholinesterase

Characterization of a Novel BCHE “Silent” Allele: Point Mutation (p.Val204Asp) Causes Loss of Activity and Prolonged Apnea with Suxamethonium

Atypical serum cholinesterase in a family with congenital distichiasis.

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