The molecular biology of the flavin-containing monooxygenases of man

Phillips, Ian; Dolphin, Colin T.; Clair, Philippe; Hadley, Mark R.; Hutt, Andrew J.; McCombie, Richard Ralph; Smith, Robert L.; Shephard, Elizabeth A.

doi:10.1016/0009-2797(94)03580-2

Cited by 134 publications

(111 citation statements)

References 28 publications

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“…We now know that humans possess five functional FMO genes (FMO1 to FMO5) [11][12][13]. FMO1 to FMO4 are clustered on chromosome 1 at q24.3 [13], along with a pseudogene, FMO6P [13,14].…”

Section: The Fmo Family Of Humansmentioning

confidence: 99%

“…The five functional FMO genes are thought to have arisen, via duplications of an ancestral gene, some 210-275 million years ago [13]. The proteins they encode have 51% to 57% amino acid sequence identity [12]. Of these, FMOs 1 and 3 have been implicated in disease and FMOs 1, 2 and 3 are the most important in the metabolism of foreign chemicals [1][2][3].…”

Section: The Fmo Family Of Humansmentioning

confidence: 99%

“…In adult humans the main site of expression of FMO1 is the kidney [12,[31][32][33]. In this organ the amount of FMO1 [33] exceeds that of the total content of CYPs [34] and approaches that observed in the liver for the major hepatic CYP CYP3A4 [35].…”

Section: Tissue Distribution and Regulation Of Expressionmentioning

confidence: 99%

“…FMO1 is, thus, likely to play an important role in the renal metabolism of drugs. The FMO1 gene is expressed in fetal human liver [12,[31][32][33]36], but its expression is extinguished just after birth [36]. Thus, in the adult human FMO1 makes no contribution to the hepatic metabolism of drugs.…”

Section: Tissue Distribution and Regulation Of Expressionmentioning

confidence: 99%

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Flavin-containing monooxygenases: mutations, disease and drug response

Phillips

Shephard

2008

Trends in Pharmacological Sciences

117

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“…We now know that humans possess five functional FMO genes (FMO1 to FMO5) [11][12][13]. FMO1 to FMO4 are clustered on chromosome 1 at q24.3 [13], along with a pseudogene, FMO6P [13,14].…”

Section: The Fmo Family Of Humansmentioning

confidence: 99%

Section: The Fmo Family Of Humansmentioning

confidence: 99%

Section: Tissue Distribution and Regulation Of Expressionmentioning

confidence: 99%

Section: Tissue Distribution and Regulation Of Expressionmentioning

confidence: 99%

See 2 more Smart Citations

Flavin-containing monooxygenases: mutations, disease and drug response

Phillips

Shephard

2008

Trends in Pharmacological Sciences

117

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“…Since those early studies, FMOs have been purified and/or cloned from multiple sources (Table 1). Until recently, it was thought that only 5 genes were expressed in mammals Lawton et al, 1994;Cashman, 1995;Phillips et al, 1995). A sixth human gene, FMO6, identified by the Sanger Center chromosome 1 sequencing project, was demonstrated to be a psuedogene .…”

Section: Introductionmentioning

confidence: 99%

Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism

Krueger

Williams

2005

Pharmacology & Therapeutics

503

444

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Flavin-containing monooxygenase (FMO) oxygenates drugs and xenobiotics containing a "softnucleophile", usually nitrogen or sulfur. FMO, like cytochrome P450 (CYP), is a monooxygenase, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate. FMO and CYP also exhibit similar tissue and cellular location, molecular weight, substrate specificity, and exist as multiple enzymes under developmental control. The human FMO functional gene family is much smaller (5 families each with a single member) than CYP. FMO does not require a reductase to transfer electrons from NADPH and the catalytic cycle of the 2 monooxygenases is strikingly different. Another distinction is the lack of induction of FMOs by xenobiotics.In general, CYP is the major contributor to oxidative xenobiotic metabolism. However, FMO activity may be of significance in a number of cases and should not be overlooked. FMO and CYP have overlapping substrate specificities, but often yield distinct metabolites with potentially significant toxicological/pharmacological consequences.The physiological function(s) of FMO are poorly understood. Three of the 5 expressed human FMO genes, FMO1, FMO2 and FMO3, exhibit genetic polymorphisms. The most studied of these is FMO3 (adult human liver) in which mutant alleles contribute to the disease known as trimethylaminuria. The consequences of these FMO genetic polymorphisms in drug metabolism and human health are areas of research requiring further exploration.

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