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

Rita J. Valentino, Oksana Lockridge, Harry W. Eckerson, Bert N. La Du

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Vmax and Km 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 Vmax substrate to Vmax 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 CaCl2 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 Km values for atypical and usual cholinesterase indicated that the positively charged substrates, as well as aspirin in the presence of CaCl2, showed a lower affinity with atypical than with usual cholinesterase, while neutral esters had nearly the same Km 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.

Original languageEnglish (US)
Pages (from-to)1643-1649
Number of pages7
JournalBiochemical Pharmacology
Volume30
Issue number12
DOIs
StatePublished - Jun 15 1981

Fingerprint

Cholinesterases
Serum
Pharmaceutical Preparations
Aspirin
Substrates
Benzoylcholine
Tetracaine
Procaine
Phenylbutyrates
In Vitro Techniques
Tromethamine
Buffers
Esters

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Prediction of drug sensitivity in individuals with atypical serum cholinesterase based on in vitro biochemical studies. / Valentino, Rita J.; Lockridge, Oksana; Eckerson, Harry W.; La Du, Bert N.

In: Biochemical Pharmacology, Vol. 30, No. 12, 15.06.1981, p. 1643-1649.

Research output: Contribution to journalArticle

@article{e0403945f9c64da985a3b0d2b7ca2ec2,
title = "Prediction of drug sensitivity in individuals with atypical serum cholinesterase based on in vitro biochemical studies",
abstract = "Vmax and Km 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 Vmax substrate to Vmax 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 CaCl2 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 Km values for atypical and usual cholinesterase indicated that the positively charged substrates, as well as aspirin in the presence of CaCl2, showed a lower affinity with atypical than with usual cholinesterase, while neutral esters had nearly the same Km 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.",
author = "Valentino, {Rita J.} and Oksana Lockridge and Eckerson, {Harry W.} and {La Du}, {Bert N.}",
year = "1981",
month = "6",
day = "15",
doi = "10.1016/0006-2952(81)90392-0",
language = "English (US)",
volume = "30",
pages = "1643--1649",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "12",

}

TY - JOUR

T1 - Prediction of drug sensitivity in individuals with atypical serum cholinesterase based on in vitro biochemical studies

AU - Valentino, Rita J.

AU - Lockridge, Oksana

AU - Eckerson, Harry W.

AU - La Du, Bert N.

PY - 1981/6/15

Y1 - 1981/6/15

N2 - Vmax and Km 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 Vmax substrate to Vmax 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 CaCl2 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 Km values for atypical and usual cholinesterase indicated that the positively charged substrates, as well as aspirin in the presence of CaCl2, showed a lower affinity with atypical than with usual cholinesterase, while neutral esters had nearly the same Km 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.

AB - Vmax and Km 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 Vmax substrate to Vmax 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 CaCl2 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 Km values for atypical and usual cholinesterase indicated that the positively charged substrates, as well as aspirin in the presence of CaCl2, showed a lower affinity with atypical than with usual cholinesterase, while neutral esters had nearly the same Km 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.

UR - http://www.scopus.com/inward/record.url?scp=0019409978&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019409978&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(81)90392-0

DO - 10.1016/0006-2952(81)90392-0

M3 - Article

C2 - 7271851

AN - SCOPUS:0019409978

VL - 30

SP - 1643

EP - 1649

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 12

ER -