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Immunological comparison of the usual and atypical human serum cholinesterase phenotypes

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Abstract

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.

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References

  • Altland, K., and Goedde, H. W. (1970). Heterogeneity in the silent gene phenotype of pseudocholinesterase of human serum.Biochem. Genet. 4321.

    Article  CAS  PubMed  Google Scholar 

  • Ashwell, G., and Morrell, A. G. (1974). The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins.Adv. Enzymol. 4199.

    CAS  PubMed  Google Scholar 

  • Bamford, K. F., and Harris, H. (1964). Studies on “usual” and “atypical” serum cholinesterase using alpha-naphthyl acetate as substrate.Ann. Hum. Genet. 27417.

    CAS  PubMed  Google Scholar 

  • Bohlen, P., Stein, S., Dairman, W., and Udenfriend, S. (1973). Fluorometric assay of proteins in the nanogram range.Arch. Biochem. Biophys. 155213.

    CAS  PubMed  Google Scholar 

  • Das, P. K. (1974). Purification of two unusual serum cholinesterase variants (CH D1 and CH D1 ) and comparison of their properties with those of normals.Enzyme 18279.

    CAS  PubMed  Google Scholar 

  • Davies, R. O., Marton, A. V., and Kalow, W. (1960). The action of normal and atypical cholinesterase of human serum upon a series of esters of choline.Can. J. Biochem. Physiol. 38545.

    CAS  PubMed  Google Scholar 

  • Garry, P. J., Dietz, A. A., Lubrano, T., Ford, P. C., James, K., and Rubinstein, H. M. (1976). New allele at cholinesterase locus 1.J. Med. Genet. 1338.

    CAS  PubMed  Google Scholar 

  • Goedde, H. W., and Altland, K. (1968). Evidence for different “silent genes” in the human serum pseudocholinesterase polymorphism.Ann. N.Y. Acad. Sci. 151540.

    CAS  PubMed  Google Scholar 

  • Goedde, H. W., Gehring, D., and Hofmann, R. A. (1965). On the problem of a “silent gene” in pseudocholinesterase polymorphism.Biochim. Biophys. Acta 107391.

    CAS  PubMed  Google Scholar 

  • Goedde, H. W., Held, K. R., and Altland, K. (1968). Hydrolysis of succinyldicholine and succinylmonocholine in human serum.Mol. Pharmacol. 4274.

    CAS  PubMed  Google Scholar 

  • Harris, H., and Whittaker, M. (1961). Differential inhibition of human serum cholinesterase with fluoride: Recognition of two new phenotypes.Nature 191496.

    CAS  PubMed  Google Scholar 

  • Harris, H., Robson, E. B., Glen-Bott, A. M. and Thornton, J. A. (1963). Evidence for non-allelism between genes affecting human serum cholinesterase.Nature 2001185.

    CAS  PubMed  Google Scholar 

  • Haupt, H., Heide, K., Zwisler, O., and Schwick, H. G. (1966). Isolierung und physikalisch-chemische Charakterisierung der Cholinesterase aus Humanserum.Blut 1465.

    Article  CAS  PubMed  Google Scholar 

  • Hofstee, B. H. J. (1951). Spectrophotometric determinations of esterases.Science 114128.

    CAS  PubMed  Google Scholar 

  • Huggins, C., and Lapides, J. (1947). Chromogenic substrates. IV. Acyl esters of p-nitrophenol as substrates for the colorimetric determination of esterase.J. Biol. Chem. 170467.

    CAS  Google Scholar 

  • Juul, P. (1968). Human plasma cholinesterase isoenzymes.Clin. Chim. Acta 19205.

    Article  CAS  PubMed  Google Scholar 

  • Kalow, W. (1962). Heritable factors recognized in man by the use of drugs. InPharmacogenetics, Heredity and the Response to Drugs W. B. Saunders, Philadelphia, pp. 69–145.

    Google Scholar 

  • Kalow, W. (1965). Contribution of hereditary factors to the response to drugs.Fed. Proc. 241259.

    CAS  PubMed  Google Scholar 

  • Kalow, W., and Davies, R. O. (1958). The activity of various esterase inhibitors toward atypical human serum cholinesterase.Biochem. Pharmacol. 1183.

    Google Scholar 

  • Kalow, W., and Genest, K. (1957). A method for the detection of atypical forms of human serum cholinesterase. Determination of dibucaine numbers.Can. J. Biochem. Physiol. 35339.

    CAS  PubMed  Google Scholar 

  • Kalow, W., and Gunn, D. R. (1957). The relation between dose of succinylcholine and duration of apnea in man.J. Pharmacol. Exp. Ther. 120203.

    CAS  PubMed  Google Scholar 

  • Kalow, W., and Lindsay, H. A. (1955). A comparison of optical and manometric methods for the assay of human serum cholinesterase.Can. J. Biochem. Physiol. 33568.

    CAS  PubMed  Google Scholar 

  • La Du, B. N. (1971). Plasma esterase activity and the metabolism of drugs with ester groups.Ann. N.Y. Acad. Sci. 179684.

    PubMed  Google Scholar 

  • La Du, B. N. (1972). Isoniazid and pseudocholinesterase polymorphisms.Fed. Proc. 311276.

    PubMed  Google Scholar 

  • Liddell, J., Lehmann, H., Davies, D., and Sharih, A. (1962). Physical separation of pseudo cholinesterase variants in human serum.Lancet 1463.

    CAS  PubMed  Google Scholar 

  • Lockridge, O., and La Du, B. N. (1978). Comparison of atypical and usual human serum cholinesterase: Purification, number of active sites, substrate affinity, and turnover number.J. Biol. Chem. 253361.

    CAS  PubMed  Google Scholar 

  • Lockridge, O., Eckerson, H. W., and La Du, B. N. (1979). Interchain disulfide bonds and subunit organization in human serum cholinesterase.J. Biol. Chem. 2548324.

    CAS  PubMed  Google Scholar 

  • Lockridge, O., Mottershaw-Jackson, N., Eckerson, H. W., and La Du, B. N. (1980). Hydrolysis of diacetylmorphine (heroin) by human serum cholinesterase.J. Pharmacol. Exp. Ther. 2151.

    CAS  PubMed  Google Scholar 

  • Lubin, A. H., Garry, P. J., Owen, G. M., Prince, L. C., and Dietz, A. A. (1973). Further variation of the “silent” cholinesterase gene.Biochem. Med. 8160.

    Article  CAS  PubMed  Google Scholar 

  • Main, A. R., Miles, K. E., and Braid, P. E. (1961). The determination of human-serum-cholinesterase activity with o-nitrophenyl butyrate.Biochem. J. 78769.

    PubMed  Google Scholar 

  • Muensch, H., Yoshida, A., Altland, K., Jensen, W., and Goedde, H. W. (1978). Structural difference at the active site of dibucaine resistant variant of human plasma cholinesterase.Am. J. Hum. Genet. 30302.

    CAS  PubMed  Google Scholar 

  • Neitlich, H. W. (1966). Increased plasma cholinesterase activity and succinylcholine resistance: A genetic variant.J. Clin. Invest. 45380.

    CAS  PubMed  Google Scholar 

  • Rubinstein, H. M., Dietz, A. A., Hodges, L. K., Lubrano, T., and Czebotar, V. (1970). Silent cholinesterase gene: Variations in the properties of serum enzyme in apparent homozygotes.J. Clin. Invest. 49479.

    CAS  PubMed  Google Scholar 

  • Rubinstein, H. M., Dietz, A. A., Lubrano, T., and Garry, P. J. (1976). E j1 , a quantitative variant at cholinesterase locus 1: Immunological evidence.J. Med. Genet. 1343.

    CAS  PubMed  Google Scholar 

  • Rubinstein, H. M., Dietz, A. A., and Lubrano, T. (1978). E k1 , another quantitative variant at cholinesterase locus 1.J. Med. Genet. 1527.

    CAS  PubMed  Google Scholar 

  • Rush, R. A., Kindler, S. H., and Udenfriend, S. (1974). Homospecific activity, an immunologic index of enzyme homogeneity; Changes during the purification of dopamine-β-hydroxylase.Biochem. Biophys. Res. Comm. 6138.

    CAS  PubMed  Google Scholar 

  • Shows, T. B., Alper, C. A., Bootsma, D., Dorf, M., Douglas, T., Huisman, T., Kit, S., Klinger, H. P., Kozak, C., Lalley, P. A., Lindsley, D., McAlpine, P. J., McDougall, J. K., Meera Khan, P., Meisler, M., Morton, N. E., Opitz, J. M., Partridge, C. W., Payne, R., Roderick, T. H., Rubinstein, P., Ruddle, F. H., Shaw, M., Spranger, J. W., and Weiss, K. (1979). International system for human gene nomenclature (1979).Cytogenet. Cell. Genet. 2596.

    CAS  PubMed  Google Scholar 

  • Simpson, N. E., and Elliott, C. R. (1981). Cholinesterase Newfoundland: A new succinylcholine-sensitive variant of cholinesterase at locus 1.Am. J. Hum. Genet. 33366.

    CAS  PubMed  Google Scholar 

  • Simpson, N. E., and Kalow, W. (1964). The “silent” gene for serum cholinesterase.Am. J. Hum. Genet. 16180.

    CAS  PubMed  Google Scholar 

  • Svensmark, O. (1961). Human serum cholinesterase as a sialo-protein.Acta Physiol. Scand. 52267.

    CAS  PubMed  Google Scholar 

  • Vaitukaitis, J., Robbins, J. B., Nieschlag, E., and Ross, G. T. (1971). A method for producing specific antisera with small doses of immunogen.J. Clin. Endocrinol. 33988.

    CAS  Google Scholar 

  • Valentino, R. J., Lockridge, O., Eckerson, H. W., and La Du, B. N. (1981). Prediction of drug sensitivity in individuals with atypical serum cholinesterase based onin vitro biochemical studies.Biochem. Pharmacol. 301643.

    Article  CAS  PubMed  Google Scholar 

  • Wetstone, H. J., and LaMotta, R. V. (1965). The clinical stability of serum cholinesterase activity.Clin. Chem. 11653.

    CAS  PubMed  Google Scholar 

  • WHO Scientific Group (1973). Pharmacogenetics.WHO Tech. Rep. Ser. 5241.

    Google Scholar 

  • Wilson, I. B., and Bergmann, F. (1950). Studies on cholinesterase. VII. The active surface of acetylcholine esterase derived from effects of pH on inhibitors.J. Biol. Chem. 186683.

    CAS  PubMed  Google Scholar 

  • Yoshida, A., and Motulsky, A. G. (1969). A pseudocholinesterase variant (E Cynthiana) associated with elevated plasma enzyme activity.Am. J. Hum. Genet. 21486.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Pharmacology Department, University of Michigan, 48109, Ann Arbor, Michigan

    Harry W. Eckerson, Allen Oseroff, Oksana Lockridge & Bert N. La Du

Authors
  1. Harry W. Eckerson
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  2. Allen Oseroff
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  3. Oksana Lockridge
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  4. Bert N. La Du
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Additional information

This work was supported by U.S. Public Health Service Grants NS 15871 and GM 27028 and by a grant from the Hoffmann-La Roche Foundation.

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Eckerson, H.W., Oseroff, A., Lockridge, O. et al. Immunological comparison of the usual and atypical human serum cholinesterase phenotypes. Biochem Genet 21, 93–108 (1983). https://doi.org/10.1007/BF02395394

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  • DOI: https://doi.org/10.1007/BF02395394

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