Hydrolytic profile for ester‐ or amide‐linkage by carboxylesterases pI 5.3 and 4.5 from human liver

DOI Web Site Web Site PubMed 被引用文献27件 参考文献23件 オープンアクセス

書誌事項

タイトル別名
  • Hydrolytic Profile for Ester- or Amide-linkage by Carboxylesterases pI 5.3 and 4.5 from Human Liver.
  • Hydrolytic Profile for Ester-or Amide-l
  • Hydrolytic profile for ester- or amide-linkage by carboxylesterase pI 5.3 and 4.5 from human liver
  • Hydrolytic profile for ester­ or amide­linkage by carboxylesterases pI 5.3 and 4.5 from human liver
  • Hydrolytic profile for ester- or amide-linkage by carboxylesterases pI 5.3 and pI 4.5 from human liver
公開日
1997
資源種別
journal article
DOI
  • 10.1248/bpb.20.869
公開者
公益社団法人 日本薬学会

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説明

Carboxylesterases (EC 3.1.1.1) from human liver were purified using Q-Sepharose, Sephadex G-150, isoelectrofocusing and Con A-Sepharose. The calculated molecular mass of the pI 5.3 enzyme was 120 kDa and 61 kDa from the results of Sephadex G-150 gel filtration and SDS-polyacrylamide gel electrophoresis (PAGE), respectively, suggesting that this enzyme is a dimer. On the other hand, carboxylesterase pI 4.5, with a molecular mass of 64 kDa, was a monomer. The activities of both enzymes were inhibited by typical serine enzyme inhibitors. Amino acid sequence analysis of the purified enzymes pI 5.3 and 4.5 showed high homology with rabbit carboxylesterase form 1 and 2, respectively. The results also suggested that carboxylesterase pI 5.3 is identical to the deduced amino acid sequence from cDNA for HU1, and that carboxylesterase pI 4.5 is identical to the deduced amino acid sequence from the cDNA registered as human carboxylesterase (hCE-2) in GenBank. We first purified carboxylesterase pI 4.5 and investigated its hydrolytic activity upon various drugs. The two enzymes differed in substrate specificity. Prodrugs of angiotensin-converting enzyme inhibitors, such as delapril and imidapril, were converted to active metabolites by carboxylesterase pI 5.3, but not by carboxylesterase pI 4.5. The hydrolysis velocity of temocapril by carboxylesterase pI 5.3 was 12-fold faster than by carboxylesterase pI 4.5. In contrast, aspirin, oxybutynin and procaine were hydrolyzed by only carboxylesterase pI 4.5. We also found that an amide-linkage in drugs, except for that in aniracetam, was not a good substrate for the two enzymes. Consequently, carboxylesterases pI 5.3 and 4.5 may be involved in the metabolism of various drugs containing an ester-linkage.

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