Title
In vitro and in vivo inhibition of human flavin-containing monooxygenase form 3 (FMO3) in the presence of dietary indoles
Author
Cashman, J.R.
Xiong, Y.
Lin, J.
Verhagen, H.
van Poppel, G.
van Bladeren, P.J.
Larsen-Su, S.
Williams, D.E.
Centraal Instituut voor Voedingsonderzoek TNO
Publication year
1999
Abstract
The effect of consumption of glucosinolate-containing Brussels sprouts on flavin-containing monooxygenase functional activity in humans was investigated in 10 healthy, male, non-smoking volunteers. After a 3-week run-in period, 5 volunteers continued on a glucosinolate-free diet for 3 weeks (control group), and 5 others consumed 300 g of cooked Brussels sprouts per day (sprouts group). Human flavin-containing monooxygenase activity was measured by determining the levels of urinary trimethylamine and trimethylamine N-oxide. In the control group similar trimethylamine to trimethylamine N-oxide ratios were observed, while in the sprouts group the trimethylamine to trimethylamine N-oxide ratios were increased 2.6- to 3.2-fold, and thus flavin-containing monooxygenase functional activity was decreased significantly. To investigate the molecular basis for the in vivo inhibition of functional human flavin-containing monooxygenase activity, in vitro studies were carried out examining the effect of acid condensation products of indole-3-carbinol, anticipated to be formed after transit of Brussels sprouts through the gastrointestinal system, on the prominent cDNA-expressed human flavin-containing monooxygenase form 3 enzymes. Two indole-containing materials were observed to be potent inhibitors of human flavin-containing monooxygenases, having K(i) values in the low micromolar range. The results suggested that acid condensation products expected to be formed upon transit of Brussels sprouts materials through the gastrointestinal system were potent competitive inhibitors of human flavin-containing monooxygenase form 3 enzymes. The findings indicate that daily intake of Brussels sprouts may lead to a decrease in human flavin-containing monooxygenase activity, and this may have consequences for metabolism of other xenobiotics or dietary constituents. Copyright (C) 1999 Elsevier Science Inc.
Subject
Nutrition
Dietary indoles
Human flavin-containing monooxygenase
Indole-3-carbinol-related inhibitors
Trimethylamine N-oxygenation inhibitors
3 indolemethanol
Complementary DNA
Flavin containing monooxygenase 3
Glucosinolate
Hydrochloric acid
Indole derivative
Isoenzyme
Trimethylamine
Trimethylamine oxide
Unclassified drug
Unspecific monooxygenase
Adult
Controlled study
Dietary intake
Enzyme activity
Enzyme inhibition
Gas chromatography
Gastrointestinal tract
High performance liquid chromatography
Human
Human experiment
Male
Mass spectrometry
Normal human
Oral drug administration
Polymerization
Priority journal
Volunteer
Xenobiotic metabolism
Adult
Antioxidants
Brassica
Carrier Proteins
Cross-Over Studies
Diet
Humans
Indoles
Male
Methylamines
Oxygenases
To reference this document use:
http://resolver.tudelft.nl/uuid:0d6f69b7-a622-4d07-bcf0-48a502fe9a81
DOI
https://doi.org/10.1016/s0006-2952(99)00166-5
TNO identifier
235157
ISSN
0006-2952
Source
Biochemical Pharmacology, 58 (6), 1047-1055
Document type
article