Metabolism of [3-14C] coumarin by human liver microsomes

M. L. P. S. van Iersel; C. J. Henderson; D. G. Walters; R. J. Price; C. R. Wolf; B. G. Lake

doi:10.3109/00498259409043279

Metabolism of [3-14C] coumarin by human liver microsomes

M. L. P. S. van Iersel, C. J. Henderson, D. G. Walters, R. J. Price, C. R. Wolf, B. G. Lake

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Abstract

1. The metabolism of 50 mu M [3-C-14] coumarin has been studied in a panel of 12 human liver microsomal samples of known P450 isoenzyme profile.

2. [3-C-14] coumarin was metabolized by human liver microsomes to various polar products including 3-, 4- and 7-hydroxycoumarins (3-HC, 4-HC and 7-HC) 6,7-dihydroxycoumarin (6,7-DiHC), o-coumaric acid (o-CA), o-hydroxyphenyl-acetaldehyde (o-HPA), o-hydroxyphenylethanol (o-HPE), o-hydroxyphenylacetic acid (o-HPAA) and o-hydroxyphenylpropionic acid (o-HPPA) and to product(s) that bind covalently to microsomal proteins.

3. For all 12 subjects, mean rates of [3-C-14] coumarin metabolism to total polar products (metabolism to all products except product(s) covalently bound to microsomal proteins), 7-HC, the 3-hydroxylation pathway (sum of 3-HC, o-HPA, o-HPE and o-HPAA), o-HPPA, 6,7-DiHC and covalent binding were 1420, 1230, 73.8, 52.5, 9.5 and 4.8 pmol/min/mg protein respectively.

4. Marked interindividual differences in [3-C-14] coumarin metabolism to total polar products (30-fold variation) and 7-HC (2250-fold variation) were observed.

5. Good correlations were observed between [3-C-14] coumarin metabolism and total polar products, 7-HC, o-HPPA and 6,7-DiHC, but not to 3-hydroxylation pathway products and levels of 2A6 and 2B6 in human liver microsomes.

6. [3-C-14] coumarin metabolism to any polar products did not correlate with levels of 1A2, 2C8, 2C9, 2E1, 3A3/4 and 4A1 in human liver microsomes.

Original language	English
Pages (from-to)	795-803
Number of pages	9
Journal	Xenobiotica
Volume	24
Issue number	8
DOIs	https://doi.org/10.3109/00498259409043279
Publication status	Published - Aug 1994

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@article{b091f1995913410ca77eeb0f0d29dba6,

title = "Metabolism of [3-14C] coumarin by human liver microsomes",

abstract = "1. The metabolism of 50 mu M [3-C-14] coumarin has been studied in a panel of 12 human liver microsomal samples of known P450 isoenzyme profile.2. [3-C-14] coumarin was metabolized by human liver microsomes to various polar products including 3-, 4- and 7-hydroxycoumarins (3-HC, 4-HC and 7-HC) 6,7-dihydroxycoumarin (6,7-DiHC), o-coumaric acid (o-CA), o-hydroxyphenyl-acetaldehyde (o-HPA), o-hydroxyphenylethanol (o-HPE), o-hydroxyphenylacetic acid (o-HPAA) and o-hydroxyphenylpropionic acid (o-HPPA) and to product(s) that bind covalently to microsomal proteins.3. For all 12 subjects, mean rates of [3-C-14] coumarin metabolism to total polar products (metabolism to all products except product(s) covalently bound to microsomal proteins), 7-HC, the 3-hydroxylation pathway (sum of 3-HC, o-HPA, o-HPE and o-HPAA), o-HPPA, 6,7-DiHC and covalent binding were 1420, 1230, 73.8, 52.5, 9.5 and 4.8 pmol/min/mg protein respectively.4. Marked interindividual differences in [3-C-14] coumarin metabolism to total polar products (30-fold variation) and 7-HC (2250-fold variation) were observed.5. Good correlations were observed between [3-C-14] coumarin metabolism and total polar products, 7-HC, o-HPPA and 6,7-DiHC, but not to 3-hydroxylation pathway products and levels of 2A6 and 2B6 in human liver microsomes.6. [3-C-14] coumarin metabolism to any polar products did not correlate with levels of 1A2, 2C8, 2C9, 2E1, 3A3/4 and 4A1 in human liver microsomes.",

author = "{van Iersel}, {M. L. P. S.} and Henderson, {C. J.} and Walters, {D. G.} and Price, {R. J.} and Wolf, {C. R.} and Lake, {B. G.}",

year = "1994",

month = aug,

doi = "10.3109/00498259409043279",

language = "English",

volume = "24",

pages = "795--803",

journal = "Xenobiotica",

issn = "0049-8254",

publisher = "Taylor & Francis",

number = "8",

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TY - JOUR

T1 - Metabolism of [3-14C] coumarin by human liver microsomes

AU - van Iersel, M. L. P. S.

AU - Henderson, C. J.

AU - Walters, D. G.

AU - Price, R. J.

AU - Wolf, C. R.

AU - Lake, B. G.

PY - 1994/8

Y1 - 1994/8

N2 - 1. The metabolism of 50 mu M [3-C-14] coumarin has been studied in a panel of 12 human liver microsomal samples of known P450 isoenzyme profile.2. [3-C-14] coumarin was metabolized by human liver microsomes to various polar products including 3-, 4- and 7-hydroxycoumarins (3-HC, 4-HC and 7-HC) 6,7-dihydroxycoumarin (6,7-DiHC), o-coumaric acid (o-CA), o-hydroxyphenyl-acetaldehyde (o-HPA), o-hydroxyphenylethanol (o-HPE), o-hydroxyphenylacetic acid (o-HPAA) and o-hydroxyphenylpropionic acid (o-HPPA) and to product(s) that bind covalently to microsomal proteins.3. For all 12 subjects, mean rates of [3-C-14] coumarin metabolism to total polar products (metabolism to all products except product(s) covalently bound to microsomal proteins), 7-HC, the 3-hydroxylation pathway (sum of 3-HC, o-HPA, o-HPE and o-HPAA), o-HPPA, 6,7-DiHC and covalent binding were 1420, 1230, 73.8, 52.5, 9.5 and 4.8 pmol/min/mg protein respectively.4. Marked interindividual differences in [3-C-14] coumarin metabolism to total polar products (30-fold variation) and 7-HC (2250-fold variation) were observed.5. Good correlations were observed between [3-C-14] coumarin metabolism and total polar products, 7-HC, o-HPPA and 6,7-DiHC, but not to 3-hydroxylation pathway products and levels of 2A6 and 2B6 in human liver microsomes.6. [3-C-14] coumarin metabolism to any polar products did not correlate with levels of 1A2, 2C8, 2C9, 2E1, 3A3/4 and 4A1 in human liver microsomes.

AB - 1. The metabolism of 50 mu M [3-C-14] coumarin has been studied in a panel of 12 human liver microsomal samples of known P450 isoenzyme profile.2. [3-C-14] coumarin was metabolized by human liver microsomes to various polar products including 3-, 4- and 7-hydroxycoumarins (3-HC, 4-HC and 7-HC) 6,7-dihydroxycoumarin (6,7-DiHC), o-coumaric acid (o-CA), o-hydroxyphenyl-acetaldehyde (o-HPA), o-hydroxyphenylethanol (o-HPE), o-hydroxyphenylacetic acid (o-HPAA) and o-hydroxyphenylpropionic acid (o-HPPA) and to product(s) that bind covalently to microsomal proteins.3. For all 12 subjects, mean rates of [3-C-14] coumarin metabolism to total polar products (metabolism to all products except product(s) covalently bound to microsomal proteins), 7-HC, the 3-hydroxylation pathway (sum of 3-HC, o-HPA, o-HPE and o-HPAA), o-HPPA, 6,7-DiHC and covalent binding were 1420, 1230, 73.8, 52.5, 9.5 and 4.8 pmol/min/mg protein respectively.4. Marked interindividual differences in [3-C-14] coumarin metabolism to total polar products (30-fold variation) and 7-HC (2250-fold variation) were observed.5. Good correlations were observed between [3-C-14] coumarin metabolism and total polar products, 7-HC, o-HPPA and 6,7-DiHC, but not to 3-hydroxylation pathway products and levels of 2A6 and 2B6 in human liver microsomes.6. [3-C-14] coumarin metabolism to any polar products did not correlate with levels of 1A2, 2C8, 2C9, 2E1, 3A3/4 and 4A1 in human liver microsomes.

U2 - 10.3109/00498259409043279

DO - 10.3109/00498259409043279

M3 - Article

SN - 0049-8254

VL - 24

SP - 795

EP - 803

JO - Xenobiotica

JF - Xenobiotica

IS - 8

ER -

Metabolism of [3-14C] coumarin by human liver microsomes

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