Cited by 245Pharmacogenetics and Drug MetabolismDrug-Induced Hepatotoxicity and ProtectionDrug Transport and Resistance Mechanisms

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Human Hepatic Flavin-Containing Monooxygenases 1 (FMO1) and 3 (FMO3) Developmental Expression

Koukouritaki, Sevasti B, Simpson, Pippa, Yeung, Catherine K, Rettie, Allan E, Hines, Ronald N·2002·Pediatric Research

DOI 10.1203/00006450-200202000-00018

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Abstract

The flavin-containing monooxygenases (FMOs) are important for the metabolism of numerous therapeutics and toxicants. Six mammalian FMO genes (FMO1-6) have been identified, each exhibiting developmental and tissue- and species-specific expression patterns. Previous studies demonstrated that human hepatic FMO1 is restricted to the fetus whereas FMO3 is the major adult isoform. These studies failed to describe temporal expression patterns, the precise timing of the FMO1/FMO3 switch, or potential control mechanisms. To address these questions, FMO1 and FMO3 were quantified in microsomal fractions from 240 human liver samples representing ages from 8 wk gestation to 18 y using Western blotting. FMO1 expression was highest in the embryo (8-15 wk gestation; 7.8 +/- 5.3 pmol/mg protein). Low levels of FMO3 expression also were detectable in the embryo, but not in the fetus. FMO1 suppression occurred within 3 d postpartum in a process tightly coupled to birth, but not gestational age. The onset of FMO3 expression was highly variable, with most individuals failing to express this isoform during the neonatal period. FMO3 was detectable in most individuals by 1-2 y of age and was expressed at intermediate levels until 11 y (12.7 +/- 8.0 pmol/mg protein). These data suggest that birth is necessary, but not sufficient for the onset of FMO3 expression. A gender-independent increase in FMO3 expression was observed from 11 to 18 y of age (26.9 +/- 8.6 pmol/mg protein). Finally, 2- to 20-fold interindividual variation in FMO1 and FMO3 protein levels were observed, depending on the age bracket.

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Authors: Koukouritaki, S. B., Simpson, P., Yeung, C. K., Rettie, A. E., & Hines, R. N.
Affiliations: Medical College of Wisconsin (US)
University of Arkansas for Medical Sciences (US)
University of Washington (US)
Corresponding author: Hines, Ronald N
ORCID: Koukouritaki, Sevasti B
Simpson, Pippa
Yeung, Catherine K
Rettie, Allan E
Hines, Ronald N
Venue: Pediatric Research
Publisher: Springer Science and Business Media LLC
Published: 2002-02
Volume: 51
Issue: 2
Pages: 236-243
ISSN: 0031-3998 (ISSN-L)
1530-0447
DOI: 10.1203/00006450-200202000-00018
OpenAlex: W2068390361
Cited by: 245
References: 66
Citations by year: 2026: 4 · 2025: 5 · 2024: 6 · 2023: 11 · 2022: 5 · 2021: 9 · 2020: 12 · 2019: 11 · 2018: 6 · 2017: 13 · 2016: 15 · 2015: 2 · 2014: 14 · 2013: 8 · 2012: 17
FWCI: 9.16
Type: journal article
Language: en
Open access: closed
Locations: Pediatric Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (CA53106, R01CA053106)
National Institute of General Medical Sciences (GM43511, GM-07750, T32GM007750)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords: flavin-containing monooxygenase, FMO1, FMO3, developmental gene expression, fetal liver, neonatal liver, age-related expression, interindividual variability, human liver microsomes, drug metabolism
MeSH terms: Adolescent, Adult, Aging, Child, Child, Preschool, Embryo, Mammalian, Female, Fetus, Gestational Age, Humans, Infant, Infant, Newborn, Isoenzymes, Liver, Male, Microsomes, Liver, Oxygenases, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Developmental

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Human Hepatic Flavin-Containing Monooxygenases 1 (FMO1) and 3 (FMO3) Developmental Expression

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