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Human Hepatic Flavin-Containing Monooxygenases 1 (FMO1) and 3 (FMO3) Developmental Expression
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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“Both mRNA and protein were found in 30% of fetal livers in the first trimester of pregnancy but not in the second and third trimesters; however, they could be detected again by 21 postnatal days.Expression of FMO3 then gradually increased to 8% of adult levels at about age nine months, 20% by 11 years, and did not reach adult levels until after 18 years (64, 133).”
From Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [64]
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Trimethylamine N -Oxide, the Microbiome, and Heart and Kidney Disease
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Self-citationDevelopmental Expression of the Major Human Hepatic CYP3A Enzymes
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Self-citation
Metadata
- 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
- Venue
- Pediatric Research
- Published
- 2002-02
- Volume
- 51
- Issue
- 2
- Pages
- 236-243
- ISSN
- 0031-3998 (ISSN-L)
- 1530-0447
- 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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