Atypical Serum Cholinesterase Research Articles

Isomeric substrate studies with normal and atypical serum cholinesterase.

Isomeric substrate studies with normal and atypical serum cholinesterase.

Prolonged Paralysis After a Test Dose of Mivacurium in a Patient with Atypical Serum Cholinesterase

Prolonged Paralysis After a Test Dose of Mivacurium in a Patient with Atypical Serum Cholinesterase

Atypical Serum Cholinesterase Eliminated by Orthotopic Liver Transplantation

Atypical Serum Cholinesterase Eliminated by Orthotopic Liver Transplantation

Atypical Serum Cholinesterase Eliminated by Orthotopic Liver Transplantation

Atypical Serum Cholinesterase Eliminated by Orthotopic Liver Transplantation

Frequencies of Atypical Serum Cholinesterase in a Mixed Population of Northeastern Brazil

Frequencies of the CHE1*A allele were estimated in 84 Whites and 772 Negroids from a random sample of Salvador, Bahia. The overall frequency of this gene in Negroids was estimated as 0.842 +/- 0.233%. This indicates that this sample presents around 50 +/- 17% of White admixture and that the estimate of the risk of developing prolonged apnoea in individuals submitted to suxamethonium is around 0.035%, that is about 1 out of 2,900.

Immunological comparison of the usual and atypical human serum cholinesterase phenotypes

Antiserum prepared against highly purified usual human serum cholinesterase (the most common phenotype) cross-reacted identically with the atypical serum cholinesterase. The level of circulating atypical enzyme protein, determined immunologically, was about 30% lower when the enzyme came from an atypical rather than a usual phenotype, and the level of enzyme activity measured enzymatically at Vmax with either o-nitrophenylbutyrate or benzoylcholine as substrate showed approximately the same degree of reduction. The average specific activity (activity at Vmax per microgram of enzyme protein) in sera from 28 usual and 20 atypical individuals did not differ significantly. These findings suggest that the atypical enzyme not only has altered catalytic properties (Km) but also might be synthesized more slowly, or cleared in vivo more rapidly, than the usual enzyme.

Immunological comparison of the usual and atypical human serum cholinesterase phenotypes

Antiserum prepared against highly purified usual human serum cholinesterase (the most common phenotype) cross-reacted identically with the atypical serum cholinesterase. The level of circulating atypical enzyme protein, determined immunologically, was about 30% lower when the enzyme came from an atypical rather than a usual phenotype, and the level of enzyme activity measured enzymatically atV max with eithero-nitrophenylbutyrate or benzoylcholine as substrate showed approximately the same degree of reduction. The average specific activity (activity atV max per microgram of enzyme protein) in sera from 28 usual and 20 atypical individuals did not differ significantly. These findings suggest that the atypical enzyme not only has altered catalytic properties (K)mbut also might be synthesized more slowly, or clearedin vivo more rapidly, than the usual enzyme.

Prediction of drug sensitivity in individuals with atypical serum cholinesterase based on in vitro biochemical studies

V max and K m values with twenty-five “atypical” and thirty-seven “usual” cholinesterase human sera were determined for the cholinesterase substrates procaine, tetracaine, benzoylcholine, o-nitro-phenylbutyrate, α-naphthylacetate and aspirin. Aspirin was demonstrated to be a substrate for serum cholinesterase. For each of these substrates the ratio of V max substrate to V max benzoylcholine was found to be similar with atypical and usual cholinesterase sera. Therefore, we concluded that the respective turnover numbers for atypical and usual cholinesterase were the same. Both atypical and usual cholinesterase sera had turnover numbers of 255 min −1 for procaine, 74 min −1 for tetracaine, 7200 min −1 for aspirin in the presence of 50 mM CaCl 2 36,000 min −1 for α-naphthylacetate, and 48,000 min −1 for o-nitrophenylbutyrate, at 25° in 0.1 M Tris-Cl buffer, pH 7.4. A comparison of K m values for atypical and usual cholinesterase indicated that the positively charged substrates, as well as aspirin in the presence of CaCl 2, showed a lower affinity with atypical than with usual cholinesterase, while neutral esters had nearly the same K m for atypical and usual cholinesterase. These results imply that individuals with atypical cholinesterase will hydrolyze therapeutic doses of positively charged substrates and aspirin at reduced rates, but neutral substrates should be hydrolyzed at normal rates.

The use of serum cholinesterase in succinylcholine apnoea.

Fifteen patients demonstrating unexpected prolonged apnoea lasting several hours after succinylcholine have been treated by a new preparation of human serum cholinesterase. Adequate spontaneous respiration was re-established in an average period of ten minutes after the injection. In 12 patients biochemical genetic examinations confirmed the presence of an atypical serum cholinesterase. In three patients none of the usual variants were found. It is therefore supposed that other unknown variants of serum cholinesterase exist which cannot hydrolyze succinylcholine. The use of serum cholinesterase in succinylcholine apnoea provided considerable relief to both patient and anaesthetist.

Atypical serum cholinesterase in a family with congenital distichiasis.

This paper describes the coexistence of genetically determined reduced cholinesterase activity and congenital distichiasis in the same family. The pedigree suggests that these two autosomal dominant diseases are segregated independently...

Atypical serum cholinesterase in the Netherlands.

Pseudocholinesterase was examined in 322 samples from unrelated, healthy blood donors. In 14 cases heterozygosity was found, i.e. the frequency of the allele for atypical cholinesterase amounts to 0.022. A comparison is made with other European populations.

GENETIC CONTROL OF THE QUANTITATIVE ACTIVITY OF A SERUM ENZYME IN MAN.

THE GENETIC CONTROL of the quantitative activity of a serum enzyme was first suggested by Augustinsson and Olsson with serum arylesterase (aryl ester hydrolase [International Union of Biochemistry 3.1.1.2] ) 1 in Swedish Landrace swine. 2 However, the authors are unaware of a report of hereditary control of the quantitative activity of a serum enzyme in man although several examples of qualitative differences exist. 3 These qualitative differences of the gene may result, of course, in gross changes in the quantitative activity of an enzyme as it acts upon a substrate. However, they do not express themselves as continuous quantitative changes in phenotype over a normal range of enzyme activity. Such qualitative differences of serum cholinesterase (acylcholine acyl-hydrolase [IUB 3.1.1.8] ) 4 in man involve the atypical serum cholinesterase first described by Kalow, 3 the C 5 extra component which is most likely nonallelic with respect to the atypical gene 5 a

Procedure for Detecting Atypical Serum Cholinesterase Using o-Nitrophenylbutyrate as Substrate

Abstract A method has been developed for demonstrating atypical serum cholinesterase by means of the self-indicating substrate, o-nitrophenylbutyrate and the inhibitor succinyldicholine. The procedure was tested for atypical cholinesterase with 76 individuals, including 5 otherwise proven homozygotes and their immediate families. In all cases, it was possible to distinguish clearly those individuals homozygous for the usual and atypical cholinesterase as well as heterozygotes.

UNUSUAL URINARY COMPOUND IN PATIENTS HOMOZYGOUS FOR HEREDITARY ATYPICAL SERUM CHOLINESTERASE.

URINE from patients homozygous for hereditary atypical serum cholinesterase (HASC) and from normals (mainly laboratory personnel) was collected and refrigerated immediately. The cholinesterase genotype, as shown in Table 1, was determined by reported methods1,2 on blood specimens drawn at the same time. The urine was lyophilized and reconstituted with distilled water to one-fifth the original volume. The concentrates were extracted by a slight modification of the method of Biran and Bartley3, as shown in Fig. 1.

THE MISMANAGEMENT OF SUXAMETHONIUM APNOEA

A case of prolonged apnoea after suxamethonium is described in which misleading evidence was obtained from studies of neuromuscular conduction with a Medilec nerve stimulator. Estimations of esterase activity, dibucaine number and fluoride number were within the range expected in individuals possessing only atypical serum cholinesterase. Electromyographic studies showed a normal response to decamethonium, but a severe and prolonged neuromuscular block after suxamethonium. The block was apparently depolarizing for at least 1½ hours. After a review of other prolonged apnoeas the role of neostigmine in the prolongation of the apnoea is highlighted, and it is suggested that the demonstration of post-tetanic facilitation does not necessarily imply that the block will be improved by anticholinesterase drugs. Two types of theory are outlined to explain this type of case, and precautions against inadvertently making matters worse are suggested.

The effect of several psychotomimetic drugs on human serum cholinesterase.

The effects of a number of drugs of psychiatric interest on human serum cholinesterase are reported. The reported occurrence of an atypical form of human serum cholinesterase, differing in sensitivity to some inhibitors, has been confirmed. LSD and BOL, both potent inhibitors of human serum cholinesterase, do not fit into any of the three groups of inhibitors defined by their relative effectiveness as inhibitors of typical and atypical human serum cholinesterase. Some of the limitations of these findings are discussed.

Some statistical data on atypical cholinesterase of human serum.

SummaryThe occurrence of atypical serum cholinesterase (pseudocholinesterase) was determined in a population which consisted of 2000 healthy persons and 2400 mental patients. The type of esterase was assessed by determining the Dibucaine Number (DN), i.e. the susceptibility of the esterase to inhibition.The distribution of DN in the population was consistent with the assumption of two autosomal allelic genes giving rise to two types of esterase. The frequency of the gene for atypical esterase in the healthy population was estimated to be 0.019 ± 0.002.The great majority of all investigated persons were of European extraction. There was no evidence for a different incidence of atypical esterase among Europeans, or between Europeans and North Americans, or between religious groups.The incidence of heterozygosity did not vary with age, sex, or body weight, although these three factors were correlated with esterase levels.There was no obvious relation between mental illness and incidence of atypical esterase but a connexion between some of the less common mental diagnoses and atypical esterase could not be excluded.