Flavin-containing monooxygenase 3 (FMO3), also known as
dimethylaniline
''N'',''N''-Dimethylaniline (DMA) is an organic chemical compound, a substituted derivative of aniline. It consists of a tertiary amine, featuring dimethylamino group attached to a phenyl group. This oily liquid is colourless when pure, but comm ...
monooxygenase
Monooxygenases are enzymes that incorporate one hydroxyl group (−OH) into substrates in many metabolic pathways. In this reaction, the two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation o ...
-oxide-forming3 and
trimethylamine
Trimethylamine (TMA) is an organic compound with the formula N(CH3)3. It is a colorless, hygroscopic, and flammable tertiary amine. It is a gas at room temperature but is usually sold as a 40% solution in water. (It is also sold in pressurized ...
monooxygenase, is a
flavoprotein
Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin.
Flavoproteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repair ...
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
() that in humans is encoded by the ''FMO3''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
This enzyme
catalyzes the following
chemical reaction
A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
, among others:
:trimethylamine + NADPH + H
+ + O
2 trimethylamine ''N''-oxide + NADP
+ + H
2O
FMO3 is the main
flavin-containing monooxygenase
The flavin-containing monooxygenase (FMO) protein family specializes in the oxidation of xeno-substrates in order to facilitate the excretion of these compounds from living organisms. These enzymes can oxidize a wide array of heteroatoms, par ...
isoenzyme In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. dif ...
that is expressed in the liver of adult humans.
The human FMO3 enzyme catalyzes several types of reactions, including: the of primary, secondary, and tertiary
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...
s;
the of
nucleophilic
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
sulfur
Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
-containing compounds;
and the of the anti-cancer agent dimethylxanthenone acetic acid (
DMXAA
Vadimezan (also known as or ASA404 and dimethylxanthone acetic acid or DMXAA) is a tumor-vascular disrupting agent (tumor-VDA) that attacks the blood supply of a cancerous tumor to cause tumor regression.
Clinical trials Non-small cell lung canc ...
).
FMO3 is the primary enzyme in humans which catalyzes the
''N''-oxidation of trimethylamine into trimethylamine ''N''-oxide;
FMO1
Dimethylaniline monooxygenase -oxide-forming1 is an enzyme that in humans is encoded by the ''FMO1'' gene.
Metabolic N-oxidation of the diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an i ...
also does this, but to a much lesser extent than FMO3.
Genetic deficiencies of the FMO3 enzyme cause
primary trimethylaminuria
Trimethylaminuria (TMAU), also known as fish odor syndrome or fish malodor syndrome, is a rare inborn error of metabolism, metabolic disorder that causes a defect in the normal production of an enzyme named flavin containing monooxygenase 3, flavi ...
, also known as "fish odor syndrome".
FMO3 is also involved in the metabolism of many
xenobiotics
A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...
(i.e., exogenous compounds which are not normally present in the body),
such as the
oxidative deamination Oxidative deamination is a form of deamination that generates α-keto acids and other oxidized products from amine-containing compounds, and occurs primarily in the liver. Oxidative deamination is stereospecific, meaning it contains different stere ...
of
amphetamine
Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
.
Table 5: N-containing drugs and xenobiotics oxygenated by FMO
br
Table 6: S-containing drugs and xenobiotics oxygenated by FMO
br
Table 7: FMO activities not involving S- or N-oxygenation
/ref>
Ligands
Cancer
FMO3 gene has been observed progressively downregulated in Human papillomavirus
Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...
-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy.
See also
*Flavin-containing monooxygenase
The flavin-containing monooxygenase (FMO) protein family specializes in the oxidation of xeno-substrates in order to facilitate the excretion of these compounds from living organisms. These enzymes can oxidize a wide array of heteroatoms, par ...
*Trimethylaminuria
Trimethylaminuria (TMAU), also known as fish odor syndrome or fish malodor syndrome, is a rare metabolic disorder that causes a defect in the normal production of an enzyme named flavin-containing monooxygenase 3 (''FMO3''). When ''FMO3'' is not w ...
References
Further reading
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External links
*
Primary Trimethylaminuria (FMO3 Deficiency)
– NCBI bookshelf GeneReviews
''GeneReviews'' is an online database containing standardized Peer review, peer-reviewed articles that describe specific heritable diseases. It was established in 1997 as ''GeneClinics'' by Roberta A Pagon (University of Washington) with funding fr ...
entry
{{Nitrogenous transferases
Amphetamine
Flavoprotein enzymes