Flavin-containing monooxygenase 3 (FMO3), also known as
dimethylaniline 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 of ...
-oxide-forming3 and
trimethylamine
Trimethylamine (TMA) is an organic compound with the formula N(CH3)3. It is a trimethylated derivative of ammonia. TMA is widely used in industry. At higher concentrations it has an ammonia-like odor, and can cause necrosis of mucous membranes ...
monooxygenase, is a
flavoprotein
Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin. These proteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repair. ...
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
() that in humans is encoded by the ''FMO3''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
This enzyme
catalyzes
Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...
the following
chemical reaction
A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...
, 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. di ...
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 organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
s;
the of
nucleophilic sulfur
Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...
-containing compounds;
and the of the anti-cancer agent dimethylxanthenone acetic acid (
DMXAA).
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 ...
also does this, but to a much lesser extent than FMO3.
Genetic deficiencies of the FMO3 enzyme cause
primary trimethylaminuria, 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 ster ...
of
amphetamine
Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...
.
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
The ''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 r ...
-positive neoplastic
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
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
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 f ...
entry
{{Nitrogenous transferases
Amphetamine
Flavoproteins