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Titolo:
PURIFICATION AND CHARACTERIZATION OF RHESUS-MONKEY LIVER AMIDO HYDROLASES AND THEIR ROLES IN THE METABOLIC POLYMORPHISM FOR E6123, A PLATELET-ACTIVATING-FACTOR RECEPTOR ANTAGONIST
Autore:
KUSANO K; SEKO T; TANAKA S; SHIKATA Y; ANDO T; IDA S; HOSOKAWA M; SATOH T; YUZURIHA T; HORIE T;
Indirizzi:
EISAI & CO LTD,DRUG METAB RES SECT,DRUG METAB & PHARMACEUT,TOKODAI 5 CHOME TSUKUBA IBARAKI 30026 JAPAN CHIBA UNIV,FAC PHARMACEUT SCI,LAB BIOCHEM PHARMACOL & BIOTOXICOL CHIBA 260 JAPAN
Titolo Testata:
Drug metabolism and disposition
fascicolo: 11, volume: 24, anno: 1996,
pagine: 1186 - 1191
SICI:
0090-9556(1996)24:11<1186:PACORL>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
ARYLACETAMIDE DEACETYLASE; PHARMACOKINETICS; HYDROXYLATION; CARCINOGENS; PROTEINS; HUMANS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
21
Recensione:
Indirizzi per estratti:
Citazione:
K. Kusano et al., "PURIFICATION AND CHARACTERIZATION OF RHESUS-MONKEY LIVER AMIDO HYDROLASES AND THEIR ROLES IN THE METABOLIC POLYMORPHISM FOR E6123, A PLATELET-ACTIVATING-FACTOR RECEPTOR ANTAGONIST", Drug metabolism and disposition, 24(11), 1996, pp. 1186-1191

Abstract

We previously showed that a polymorphism for E6123 )-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8, 3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a] [1,4]diazepine] metabolism existsonly in rhesus monkeys. In the present study, we purified, from rhesus monkey hepatic microsomes, three amido hydrolases that are involved in the metabolic polymorphism. Two forms of amido hydrolase from an extensive metabolizer and one from a poor metabolizer were purified by Q-Sepharose Fast Flow, Red A-agarose, octylamino-Sepharose 4B, and hydroxyapatite-Ultrogel chromatography, after solubilization with Lubrol. The three purified enzymes had the same molecular mass (47 kDa), and their amino-terminal amino acid sequences were identical. The enzymes were different from various known carboxylesterases in terms of substrate specificity, molecular mass, and amino-terminal amino acid sequence. They resembled arylacetamide deacetylase from human hepatic microsomes with respect to molecular mass and amino-terminal amino acid sequence. The K-M values of the high and low affinity enzymes in the extensive metabolizer and the sole enzyme in the poor metabolizer were 37.6, 73.0, and 76.5 mu M, respectively. The V-max values were 3312.4, 504.8, and 427.9 pmol/min/mg of protein, respectively. The high affinity enzyme in extensive metabolizer appears to be quite distinct, whereas the low affinity enzyme in extensive metabolizer is similar or identicalto the sole enzyme in poor metabolizer. Thus, the metabolic polymorphism in rhesus monkey may depend upon the existence of the high affinity enzyme in extensive metabolizer.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 18:33:27