Mouse hepatic microsomal enzyme that catalyzes oxidation of 11-oxo-Δ8-tetrahydrocannabinol to Δ8-tetrahydrocannabinol-11-oic acid

K. Watanabe, N. Hirahashi, S. Narimatsu, I. Yamamoto, H. Yoshimura

Research output: Contribution to journalArticle

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Abstract

Mouse hepatic microsomes oxidized 11-oxo-Δ8-tetrahydrocannabinol (11-oxo-Δ8-THC, aldehyde) to Δ8-THC-11-oic-acid (carboxylic acid). The reaction required NADPH and molecular oxygen and showed an optimal pH around 7.5. The activity of NADPH-dependent carboxylic acid formation was mainly localized in microsomes. The reaction was inhibited by various inhibitors of cytochrome P-450-dependent oxidation such as SKF 525-A, α-naphthoflavone, and metyrapone. Disulfiram and menadione also inhibited the microsomal oxidation of the aldehyde to the carboxylic acid, but pyrazole did not inhibit the reaction. The pretreatment of mice with phenobarbital significantly increased the oxidation activity on the basis of microsomal protein, but did not affect it on the basis of cytochrome P-450 content. The mechanism for the oxidation of aldehyde to the carboxylic acid was confirmed to be oxygenation, since oxygen-18 was incorporated into Δ8-THC-11-oic acid from molecular oxygen during the hepatic microsomal oxidation of 11-oxo-Δ8-THC.

Original languageEnglish
Pages (from-to)218-221
Number of pages4
JournalDrug Metabolism and Disposition
Volume19
Issue number1
Publication statusPublished - 1991
Externally publishedYes

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Dronabinol
Carboxylic Acids
Aldehydes
Oxidation
Acids
Liver
Enzymes
Oxygen
Microsomes
NADP
Molecular oxygen
Proadifen
Metyrapone
Disulfiram
Vitamin K 3
Phenobarbital
Oxygenation
Cytochrome P-450 Enzyme System
Proteins
11-oxo-delta(8)-tetrahydrocannabinol

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Mouse hepatic microsomal enzyme that catalyzes oxidation of 11-oxo-Δ8-tetrahydrocannabinol to Δ8-tetrahydrocannabinol-11-oic acid. / Watanabe, K.; Hirahashi, N.; Narimatsu, S.; Yamamoto, I.; Yoshimura, H.

In: Drug Metabolism and Disposition, Vol. 19, No. 1, 1991, p. 218-221.

Research output: Contribution to journalArticle

Watanabe, K, Hirahashi, N, Narimatsu, S, Yamamoto, I & Yoshimura, H 1991, 'Mouse hepatic microsomal enzyme that catalyzes oxidation of 11-oxo-Δ8-tetrahydrocannabinol to Δ8-tetrahydrocannabinol-11-oic acid', Drug Metabolism and Disposition, vol. 19, no. 1, pp. 218-221.
Watanabe, K. ; Hirahashi, N. ; Narimatsu, S. ; Yamamoto, I. ; Yoshimura, H. / Mouse hepatic microsomal enzyme that catalyzes oxidation of 11-oxo-Δ8-tetrahydrocannabinol to Δ8-tetrahydrocannabinol-11-oic acid. In: Drug Metabolism and Disposition. 1991 ; Vol. 19, No. 1. pp. 218-221.
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abstract = "Mouse hepatic microsomes oxidized 11-oxo-Δ8-tetrahydrocannabinol (11-oxo-Δ8-THC, aldehyde) to Δ8-THC-11-oic-acid (carboxylic acid). The reaction required NADPH and molecular oxygen and showed an optimal pH around 7.5. The activity of NADPH-dependent carboxylic acid formation was mainly localized in microsomes. The reaction was inhibited by various inhibitors of cytochrome P-450-dependent oxidation such as SKF 525-A, α-naphthoflavone, and metyrapone. Disulfiram and menadione also inhibited the microsomal oxidation of the aldehyde to the carboxylic acid, but pyrazole did not inhibit the reaction. The pretreatment of mice with phenobarbital significantly increased the oxidation activity on the basis of microsomal protein, but did not affect it on the basis of cytochrome P-450 content. The mechanism for the oxidation of aldehyde to the carboxylic acid was confirmed to be oxygenation, since oxygen-18 was incorporated into Δ8-THC-11-oic acid from molecular oxygen during the hepatic microsomal oxidation of 11-oxo-Δ8-THC.",
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