METABOLISM OF TERRITREM A BY LIVER MICROSOMES OF WISTAR RATS: IDENTIFICATION OF THE METABOLITES AND THEIR METABOLIC SEQUENCE

Author: Peng Fu-Chuo   Wu Shiuan-Woei Lin   Wag Bow-Long  

Publisher: Taylor & Francis Ltd

ISSN: 1087-2620

Source: Journal of Toxicology and Environmental Health, Vol.64, Iss.7, 2001-12, pp. : 579-592

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Abstract

The metabolism of territrem A (TRA) was investigated in liver microsomes of male Wistar rats. The results indicated that three metabolites were produced from TRA and these metabolic reactions were inhibited by metyrapone, an inhibitor of cytochrome P450. Based on analysis by high-performance liquid chromatography (HPLC), mass, and nuclear magnetic resonance (NMR) spectroscopic techniques, the structure of these metabolites were identified as 4β-hydroxymethyl-4β-demethylterritrem A (MA1), 4βoxo-4β-demethylterritrem A (MAX), and 2-dihydro-4β-demethylterritrem A (MA ). It 2 was proposed that reactions proceeded by three sequential oxidative reactions in the pyran moiety of TRA: first, hydroxylation at the 4β-C methyl group of TRA to form MA1; second, oxidation at the 4β-C hydroxyl group of MA to form MAX; and third, decar1 bonylation at the 4β-C oxo group of MAX to form MA2.

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