Hydrolysis of Synthetic Substrate, L-Pyroglutamyl p-Nitroanilide is Catalyzed Solely by Pyroglutamyl Aminopeptidase I in Rat Liver Cytosol(Biochemistry/Molecular Biology)

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概要

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• Pyroglutamyl aminopeptidase I (PAP-I) is a cytosolic cysteine peptidase, which hydrolytically removes the L-pyroglutamate residue from the amino terminus of endogenous proteins and peptides. L-Pyroglutamyl p-nitroanilide serves as the synthetic substrate of this enzyme, while there is a possibility of other hydrolases being involved in the hydrolysis of this xenobiotic substrate. We cloned a full-length cDNA encoding rat PAP-I from a rat liver cDNA library and expressed this cDNA in Escherichia coli to obtain a recombinant PAP-I as a single protein. The cDNA encoded a sequence of 209 amino acids with a calculated molecular weight of 22913 Da. The homology of the deduced amino acid sequence of rat PAP-I was 98.6 and 94.3% to mouse and human PAP-Is, respectively. The biochemical properties of the recombinant rat PAP-I were almost identical to those of the recombinant mouse and human PAP-Is and the purified rat liver cytosolic PAP-I in terms of the molecular weight, subunit structure, affinity to the substrate, inhibitor profile and pH optimum. Immunoblot analysis using an antibody raised against recombinant rat PAP-I showed that rat PAP-I is present almost exclusively in the cytosolic fraction of the rat liver. Moreover, the hydrolyzing activity for L-pyroglutamyl p-nitroanilide in rat liver cytosolic fraction was completely inhibited by the antibody, strongly suggesting that this xenobiotic substrate is hydrolyzed solely by PAP-I.

• 社団法人日本薬学会の論文
• 2003-11-01

著者

• Yamada Makiko

  San-ei Gen F.f.i. Inc.

• Yamada M

  Pharmaceutical Research Division Takeda Pharmaceutical Company Limited

• Ikeda T

  Pharmacokinetics And Drug Delivery Research Laboratories Sankyo Co. Ltd.

• ABE Koji

  Pharmacokinetics and Drug Delivery Research Laboratories, Sankyo Co., Ltd.

• WATANABE Nobuaki

  Pharmacokinetics and Drug Delivery Research Laboratories, Sankyo Co., Ltd.

• KOSAKA Toshiyuki

  Biomedical Research Laboratories, Sankyo Co., Ltd.

• YAMADA Makiko

  Pharmacokinetics and Drug Delivery Research Laboratories, Sankyo Co., Ltd.

• TOKUI Taro

  Pharmacokinetics and Drug Delivery Research Laboratories, Sankyo Co., Ltd.

• IKEDA Toshihiko

  Pharmacokinetics and Drug Delivery Research Laboratories, Sankyo Co., Ltd.

• Yoshida M

  Tohoku Univ. Sendai Jpn

• Watanabe Nobuaki

  Drug Metabolism And Pharmacokinetics Research Laboratories Daiichi-sankyo Co. Ltd.

• Watanabe N

  Pharmacokinetics And Drug Delivery Research Laboratories Sankyo Co. Ltd.

• Watanabe Naomi

  Department Of Analytical Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Watanabe Nobuaki

  Pharmacokinetics And Drug Delivery Research Laboratories Sankyo Co. Ltd.

• Ikeda Toshihiko

  Pharmacokinetics And Drug Delivery Research Laboratories Sankyo Co. Ltd.

• Tokui T

  Drug Metabolism And Pharmacokinetics Research Laboratories Sankyo Co. Ltd.

• Tokui Taro

  Pharmacokinetics And Drug Delivery Research Laboratories Sankyo Co. Ltd.

• Abe K

  Drug Metabolism And Pharmacokinetics Research Laboratories Sankyo Co. Ltd.

• Kosaka Toshiyuki

  Biomedical Research Laboratories Sankyo Co. Ltd.

• Kosaka Toshiyuki

  Core Technol. Res. Laboratories Sankyo Co. Ltd.

• Yamada Makiko

  Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited

• Watanabe Nobuaki

  Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi-Sankyo Co., Ltd.

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