Cholinesterases variants

Mivacurium block is significantly prolonged in patients with inherited homozygous silent or atypical plasma cholinesterase variants the... 

Whittaker M. Plasma cholinesterase variants and the anaesthetist. Anaesthesia 1980 35 174-97. Zhang M-Q. Drug-specific cyclodextrins the future of rapid neuromuscular block reversal Drugs of the Future 2003 28 347-54. 

Harris, H., and M. Whittaker. 1962. The serum cholinesterase variants. A study of twenty-two families selected via the "intermediate" phenotype. Ann. Hum. Genet. 26 59-72. 

Whittaker, M. (1980). Plasma cholinesterase variants and the anaesthesist. Anaesthesia 35 174-97. 

Whittaker M. Plasma cholinesterase variants and the anaesthetist. Anaesthesia 1980 35(2) 174-97. 

Whittaker M, Spencer R. Plasma cholinesterase variants in patients having lithium therapy. Clin Chim Acta 1977 75(3) 421-5. 

In examining the effect of sodium chloride on cholinesterase variants, Whittaker (WIO, Wll) reported the probable existence of two new phenotypes that differ in their sensitivity to inhibition by chloride ion. Wo individuals (DN = 80-81, FN = 60-63, and chloride number ... 

However, the situation concerning silent cholinesterase variants is rather complex, and some conclusions that have been drawn may be incorrect. Some reports have stated that no enzyme activity and no cholinesterase-like protein could be detected in the silent sera studied, but it is clear that whether or not any cholinesterase activity is observed depends on a number of factors. If the gene and all of its alleles are absent, no protein product will be produced, and the phenotype will be silent under all assay conditions. The same holds true if a gene is present... 

Additional evidence concerning the heterogeneity of homozygous silent sera has been reported by Lubin et al. (L36), who studied two patients whose silent cholinesterases were different from one another and were unlike any of those reported by Rubinstein et al. (Rll). Two other patients with dissimilar silent cholinesterases were studied by Das (D2). Arnason et al. (All) have also reported on a possible nearly silent cholinesterase variant. It is difficult to compare these results with those of previous workers because of differences in experimental procedures. 

In summary, the situation concerning the silent or near silent cholinesterase variants is complex. There are at least three cholinesterase variants which are most importantly characterized by a severe quantitative deficiency in cholinesterase activity. Family studies indicate that these three variant are alleles of the gene for usual cholinesterase, Ey, although more studies are needed in this area. There are indications that a variety of other near-silent cholinesterase subtypes exist. Cases of true silence, because the gene is absent or because it produces no protein product, appear to be very rare. Many cases reported to have no cholinesterase activity have subsequently been found to have at least a trace of activity when studied imder more sensitive assay conditions or with a different substrate. 

There are reports that still other types of cholinesterase variants can be identified by electrophoretic studies. In most cases, it has not been determined whether these are genetically determined variants or acquired variants. Most of these variants have been detected by electrophoresis in a sieving gel such as starch or polyacrylamide. However, it must always be kept in mind that two new slow-migrating bands are detectable after performing two-dimensional electrophoresis on serum that has been stored (H6). The first band appears after storage for about 10 days at either 4°C... 

Van Ros and Druet (V2) reported the discovery of a slow-migrating cholinesterase variant, which they named Cg, in the sera of four African subjects. Although this may be a hereditary trait, its familial nature has not been demonstrated. These same authors also studied by two-dimensional electrophoresis two other Africans who each had a pair of additional slow bands which were called and C. Again, the possibility that these may be genetic in origin has not been demonstrated. None of these three bands is identical to those which were identified as the fetal band or storage bands by Harris et al. (H6). 

Succinylcholine Apnea and the Cholinesterase Variants Coded for by Genes at the E, Locus... 

Recommended procedures for collecting and storing plasma and serum specimens and laboratory procedures used for distinguishing the more common serum cholinesterase variants are discussed in Section 6. 

Benzoylcholine has also been used as substrate in stud)dng the effects of alkanols on human serum cholinesterase variants (W8, W9). Increasing concentrations of alkanols were found to activate the usual enzyme up to a maximum, which increased in magnitude as the chain length of the alkyl group increased. At higher concentrations, irreversible inactivation, presumably due to denaturation, occurred. The atypical enzyme was much more readily inactivated with all the alkanols, and only slight ac-tivation was observed at low alkanol concentrations. 

Cholinesterase Variants in Plasma Specimens Submitted fob Testing by Anesthetists Summaby Findings ... 

In determining the type of cholinesterase variant present in a given specimen, the ideal situation would be one in which a single, simple test would detect and identify all variant forms of the enzyme. No such test currently exists for the serum cholinesterase variants. In fact, it is not even known how many different kinds of cholinesterase variants exist in the human population. It has often been noted that the range of serum... 

Several compounds of different classes have been found to be inhibitors and/or activators of serum cholinesterase, and to be useful for distinguishing among some of the cholinesterase variants. These include inorganic anions, tertiary amines, quaternary ammonium compounds, alkyl alcohols, organophosphorus compounds, and carbamates. However, only a few compounds have been extensively used in many laboratories to distinguish variants. 

Differentiation based on dibucaine inhibition. The most commonly used agent for differentiating serum cholinesterase variants is dibucaine, which acts as an inhibitor of the enzyme (Sections 2.2 and 6.2). Its use for the differentiation of cholinesterase variants was first introduced by Kalow and Genest (Kll) in 1957, and it has been and continues to be extensively used for this purpose. The assay is performed in two cuvettes, one with substrate alone and one with substrate plus dibucaine. Both cuvettes contain M/15 phosphate buffer (Sorensen) at pH 7.4 and 5 X 10 mol/liter benzoylcholine chloride. One of the cuvettes contains 1 X 10 mol/liter dibucaine. The initial velocity at 26°C is measured in both cuvettes by determining the rate of change of absorbance at 240 nm. The dibucaine number, DN, is the percentage of inhibition by dibucaine, and is calculated as DN = 100 (v - t> )/o, where V is the uninhibited velocity and v is the velocity measured in the presence of the inhibitor. DN values obtained by this method for the most widely studied cholinesterase variants are presented in Table 1 (see Section 2.1). 

Differentiation based on fluoride inhibition. None of the reported methods utilizing dibucaine as an inhibitor is capable of differentiating all the known cholinesterase variants. Therefore, fluoride ion is also commonly used to help distinguish the genetic variants. When... 

Comments on a Selected Method for Identification OF Serum Cholinesterase Variants... 

A procedure for identifying certain cholinesterase variants was proposed by Dietz et al. (D15). After a period during which comments and discussion were offered by others working in the field, the method was published in Selected Methods of Clinical Chemistry (D16). This method is based upon the Ellman reaction (ElO), which was used by Ellman et al. (Ell) for the assay of acetylcholinesterase, and by Garry and Routh (G9) for the assay of serum cholinesterase. In these assay procedures, a thiocholine ester is used as the substrate. The thiocholine produced upon hydrolysis reacts with 5,5 -dithiobis(2-nitrobenzoic acid) (DTNB) to yield 5-thio-2-nitrobenzoate anion and other products. The rate of the reaction may be determined by measuring the rate at which... 

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