Metabolism of territrem a by liver microsomes of Wistar rats: identification of the metabolites and their metabolic sequence.
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 P-450. 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 4beta-hydroxymethyl-4beta-demethylterritrem A (MA1), 4beta-oxo-4beta-demethylterritrem A (MAX), and 2-dihydro-4beta-demethylterritrem A (MA2). It was proposed that reactions proceeded by three sequential oxidative reactions in the pyran moiety of TRA: first, hydroxylation at the 4beta-C methyl group of TRA to form MA1; second, oxidation at the 4beta hydroxyl group of MA, to form MAX; and third, decarbonylation at the 4beta-C oxo group of MAX to form MA2.
Peng
F C
FC
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Republic of China. fcpeng@ha.mc.ntu.edu.tw
Wu
S W
SW
Wag
B L
BL
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D005516:Food Microbiology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism*; D012275:Oryza / Q000382:microbiology; D011714:Pyrans / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013624:Taiwan
D000963:Antimetabolites; D011714:Pyrans; C040404:territrem A; D008797:Metyrapone