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 o ...
-oxide-forming3 and
trimethylamine monooxygenase, is a
flavoprotein 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 ...
() 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 b ...
.
This enzyme
catalyzes the following
chemical reaction
A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and breaking ...
, among others:
:trimethylamine + NADPH + H
+ + O
2 trimethylamine ''N''-oxide + NADP
+ + H
2O
FMO3 is the main
flavin-containing monooxygenase isoenzyme 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 Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...
s;
the of
nucleophilic 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 formul ...
-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;
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 comp ...
(i.e., exogenous compounds which are not normally present in the body),
such as the
oxidative deamination of
amphetamine.
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 r ...
-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy.
See also
* Flavin-containing monooxygenase
* Trimethylaminuria
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
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