Hydrolysis of carbonates, thiocarbonates, carbamates, and carboxylic esters of α-naphthol, β-naphthol, and p-nitrophenol by human, rat, and mouse liver carboxylesterases

T. L. Huang, A. Szekacs, T. Uematsu, E. Kuwano, A. Parkinson, B. D. Hammock

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Thirty carbonates, thiocarbonates, carbamates, and carboxylic esters of α-naphthol, β-naphthol, and p-nitrophenol were synthesized and tested as substrates for liver carboxylesterases from the crude microsomal fractions of human and mouse, and purified isozymes, hydrolases A and B, from rat liver microsomes. The carbonates, thiocarbonates, and carboxylic esters of α-naphthol were cleaved more rapidly than the corresponding β-naphthol isomers by the mammalian liver esterases. α-Naphthyl esters of acetic, propionic, and butyric acids were among the best substrates tested for these enzymes. The majority of the substrates was consistently hydrolyzed at higher rates by hydrolase B compared with hydrolase A, although the Michaelis-Menten constant (K(m)) values of selected substrates differed widely with these two isozymes. Malathion was a 15-fold better substrate for hydrolase B than for hydrolase A. Compared with the corresponding carboxylates, the carbonate moiety of α- and β-naphthol and p-nitrophenol lowered the specific activities of the enzymes by about fivefold but improved stability under basic conditions. The optimum pH of mouse liver esterase with the acetate, methylcarbonate, and ethylthiocarbonate of α-naphthol was between pH 7.0 and pH 7.6. Human and mouse liver microsomal esterase activities were about five orders of magnitude lower than the esterase activities of purified rat liver hydrolase B. A relationship between the catalytic activity of the enzymes and the lipophilicity of the naphthyl substrates indicated that (i) in the α- and β-naphthyl carbonate series, an inverse relationship between enzyme activity and lipophilicity of the substrates was observed, whereas (ii) in the α-naphthyl carboxylate series, an increase in enzyme activity with increasing lipophilicity of the substrates up to a logP value of about 4.0 was observed, after which the enzyme activity decreased.

Original languageEnglish (US)
Pages (from-to)639-648
Number of pages10
JournalPharmaceutical Research
Volume10
Issue number5
DOIs
StatePublished - 1993

Fingerprint

Carboxylic Ester Hydrolases
Naphthols
Carbamates
Carbonates
Liver
Rats
Hydrolysis
Esters
Hydrolases
Substrates
Esterases
Enzymes
Enzyme activity
Isoenzymes
Acetylesterase
Malathion
Propionates
Liver Microsomes
Acetic Acid
4-nitrophenol

Keywords

  • α- and β-naphthyl substrates
  • carboxylesterases
  • esterase assay, in microtiter plate
  • hydrolases A and B
  • mammalian liver
  • p-nitrophenol substrates

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

Hydrolysis of carbonates, thiocarbonates, carbamates, and carboxylic esters of α-naphthol, β-naphthol, and p-nitrophenol by human, rat, and mouse liver carboxylesterases. / Huang, T. L.; Szekacs, A.; Uematsu, T.; Kuwano, E.; Parkinson, A.; Hammock, B. D.

In: Pharmaceutical Research, Vol. 10, No. 5, 1993, p. 639-648.

Research output: Contribution to journalArticle

Huang, T. L. ; Szekacs, A. ; Uematsu, T. ; Kuwano, E. ; Parkinson, A. ; Hammock, B. D. / Hydrolysis of carbonates, thiocarbonates, carbamates, and carboxylic esters of α-naphthol, β-naphthol, and p-nitrophenol by human, rat, and mouse liver carboxylesterases. In: Pharmaceutical Research. 1993 ; Vol. 10, No. 5. pp. 639-648.
@article{f0ed829150934b02af25934262f8ae9a,
title = "Hydrolysis of carbonates, thiocarbonates, carbamates, and carboxylic esters of α-naphthol, β-naphthol, and p-nitrophenol by human, rat, and mouse liver carboxylesterases",
abstract = "Thirty carbonates, thiocarbonates, carbamates, and carboxylic esters of α-naphthol, β-naphthol, and p-nitrophenol were synthesized and tested as substrates for liver carboxylesterases from the crude microsomal fractions of human and mouse, and purified isozymes, hydrolases A and B, from rat liver microsomes. The carbonates, thiocarbonates, and carboxylic esters of α-naphthol were cleaved more rapidly than the corresponding β-naphthol isomers by the mammalian liver esterases. α-Naphthyl esters of acetic, propionic, and butyric acids were among the best substrates tested for these enzymes. The majority of the substrates was consistently hydrolyzed at higher rates by hydrolase B compared with hydrolase A, although the Michaelis-Menten constant (K(m)) values of selected substrates differed widely with these two isozymes. Malathion was a 15-fold better substrate for hydrolase B than for hydrolase A. Compared with the corresponding carboxylates, the carbonate moiety of α- and β-naphthol and p-nitrophenol lowered the specific activities of the enzymes by about fivefold but improved stability under basic conditions. The optimum pH of mouse liver esterase with the acetate, methylcarbonate, and ethylthiocarbonate of α-naphthol was between pH 7.0 and pH 7.6. Human and mouse liver microsomal esterase activities were about five orders of magnitude lower than the esterase activities of purified rat liver hydrolase B. A relationship between the catalytic activity of the enzymes and the lipophilicity of the naphthyl substrates indicated that (i) in the α- and β-naphthyl carbonate series, an inverse relationship between enzyme activity and lipophilicity of the substrates was observed, whereas (ii) in the α-naphthyl carboxylate series, an increase in enzyme activity with increasing lipophilicity of the substrates up to a logP value of about 4.0 was observed, after which the enzyme activity decreased.",
keywords = "α- and β-naphthyl substrates, carboxylesterases, esterase assay, in microtiter plate, hydrolases A and B, mammalian liver, p-nitrophenol substrates",
author = "Huang, {T. L.} and A. Szekacs and T. Uematsu and E. Kuwano and A. Parkinson and Hammock, {B. D.}",
year = "1993",
doi = "10.1023/A:1018987111362",
language = "English (US)",
volume = "10",
pages = "639--648",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "5",

}

TY - JOUR

T1 - Hydrolysis of carbonates, thiocarbonates, carbamates, and carboxylic esters of α-naphthol, β-naphthol, and p-nitrophenol by human, rat, and mouse liver carboxylesterases

AU - Huang, T. L.

AU - Szekacs, A.

AU - Uematsu, T.

AU - Kuwano, E.

AU - Parkinson, A.

AU - Hammock, B. D.

PY - 1993

Y1 - 1993

N2 - Thirty carbonates, thiocarbonates, carbamates, and carboxylic esters of α-naphthol, β-naphthol, and p-nitrophenol were synthesized and tested as substrates for liver carboxylesterases from the crude microsomal fractions of human and mouse, and purified isozymes, hydrolases A and B, from rat liver microsomes. The carbonates, thiocarbonates, and carboxylic esters of α-naphthol were cleaved more rapidly than the corresponding β-naphthol isomers by the mammalian liver esterases. α-Naphthyl esters of acetic, propionic, and butyric acids were among the best substrates tested for these enzymes. The majority of the substrates was consistently hydrolyzed at higher rates by hydrolase B compared with hydrolase A, although the Michaelis-Menten constant (K(m)) values of selected substrates differed widely with these two isozymes. Malathion was a 15-fold better substrate for hydrolase B than for hydrolase A. Compared with the corresponding carboxylates, the carbonate moiety of α- and β-naphthol and p-nitrophenol lowered the specific activities of the enzymes by about fivefold but improved stability under basic conditions. The optimum pH of mouse liver esterase with the acetate, methylcarbonate, and ethylthiocarbonate of α-naphthol was between pH 7.0 and pH 7.6. Human and mouse liver microsomal esterase activities were about five orders of magnitude lower than the esterase activities of purified rat liver hydrolase B. A relationship between the catalytic activity of the enzymes and the lipophilicity of the naphthyl substrates indicated that (i) in the α- and β-naphthyl carbonate series, an inverse relationship between enzyme activity and lipophilicity of the substrates was observed, whereas (ii) in the α-naphthyl carboxylate series, an increase in enzyme activity with increasing lipophilicity of the substrates up to a logP value of about 4.0 was observed, after which the enzyme activity decreased.

AB - Thirty carbonates, thiocarbonates, carbamates, and carboxylic esters of α-naphthol, β-naphthol, and p-nitrophenol were synthesized and tested as substrates for liver carboxylesterases from the crude microsomal fractions of human and mouse, and purified isozymes, hydrolases A and B, from rat liver microsomes. The carbonates, thiocarbonates, and carboxylic esters of α-naphthol were cleaved more rapidly than the corresponding β-naphthol isomers by the mammalian liver esterases. α-Naphthyl esters of acetic, propionic, and butyric acids were among the best substrates tested for these enzymes. The majority of the substrates was consistently hydrolyzed at higher rates by hydrolase B compared with hydrolase A, although the Michaelis-Menten constant (K(m)) values of selected substrates differed widely with these two isozymes. Malathion was a 15-fold better substrate for hydrolase B than for hydrolase A. Compared with the corresponding carboxylates, the carbonate moiety of α- and β-naphthol and p-nitrophenol lowered the specific activities of the enzymes by about fivefold but improved stability under basic conditions. The optimum pH of mouse liver esterase with the acetate, methylcarbonate, and ethylthiocarbonate of α-naphthol was between pH 7.0 and pH 7.6. Human and mouse liver microsomal esterase activities were about five orders of magnitude lower than the esterase activities of purified rat liver hydrolase B. A relationship between the catalytic activity of the enzymes and the lipophilicity of the naphthyl substrates indicated that (i) in the α- and β-naphthyl carbonate series, an inverse relationship between enzyme activity and lipophilicity of the substrates was observed, whereas (ii) in the α-naphthyl carboxylate series, an increase in enzyme activity with increasing lipophilicity of the substrates up to a logP value of about 4.0 was observed, after which the enzyme activity decreased.

KW - α- and β-naphthyl substrates

KW - carboxylesterases

KW - esterase assay, in microtiter plate

KW - hydrolases A and B

KW - mammalian liver

KW - p-nitrophenol substrates

UR - http://www.scopus.com/inward/record.url?scp=0027318905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027318905&partnerID=8YFLogxK

U2 - 10.1023/A:1018987111362

DO - 10.1023/A:1018987111362

M3 - Article

C2 - 8321828

AN - SCOPUS:0027318905

VL - 10

SP - 639

EP - 648

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 5

ER -