Purification and characterization of pranlukast hydrolase from rat liver microsomes: the hydrolase is identical to carboxylesterase pI 6.2.

Abstract:

:Two carboxylesterases with pI 6.0 and 6.2 derived from rat liver microsomes were purified. The two isozymes were remarkably different in substrate specificity, but they had equal enzymatic activity for alpha-naphthyl acetate and were inhibited equally by phenylmethylsulfonyl fluoride (PMSF) and bis-(4-nitrophenyl) phosphate (BNPP). Carboxylesterases pI 6.0 and 6.2 are identical to the enzymes referred to as hydrolase A and B, respectively, from the results of amino acid sequence analyses. Pranlukast was effectively hydrolyzed by carboxylesterase pI 6.2 but not by the pI 6.0 enzyme, and the difference in the pranlukast metabolism between the human and the rat could be explained by the substrate specificity of carboxylesterase. Furthermore, prodrugs of angiotensin converting enzyme inhibitors were found to be converted to the active drugs after hydrolysis by the carboxylesterases pI 6.0 and 6.2. Carboxylesterases generally catalyze the hydrolysis of ester-type drugs preferentially rather than amide-type drugs.

journal_name

Biol Pharm Bull

authors

Luan L,Sugiyama T,Takai S,Usami Y,Adachi T,Katagiri Y,Hirano K

doi

10.1248/bpb.20.71

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

71-5

issue

1

eissn

0918-6158

issn

1347-5215

journal_volume

20

pub_type

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