Flavoproteins are
proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respondi ...
that contain a
nucleic acid
Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main ...
derivative of
riboflavin
Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved in e ...
.
Flavoproteins are involved in a wide array of biological processes, including removal of
radicals
Radical may refer to:
Politics and ideology Politics
*Radical politics, the political intent of fundamental societal change
*Radicalism (historical), the Radical Movement that began in late 18th century Britain and spread to continental Europe and ...
contributing to oxidative stress,
photosynthesis
Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemical energy is stored i ...
, and
DNA repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
. The flavoproteins are some of the most-studied families of enzymes.
Flavoproteins have either FMN or FAD (
flavin adenine dinucleotide
Flavin may refer to:
Placename
* Flavin, Aveyron, a commune in southern France
Surname
* Adrian Flavin (born 1979), a professional rugby player
* Christopher Flavin, president of the Worldwatch Institute
* Dan Flavin (1933–1996), a minimali ...
) as a prosthetic group or as a
cofactor. The flavin is generally tightly bound (as in
adrenodoxin reductase, wherein the FAD is buried deeply).
About 5-10% of flavoproteins have a covalently linked FAD. Based on the available structural data, FAD-binding sites can be divided into more than 200 different types.
90 flavoproteins are encoded in the human genome; about 84% require FAD, and around 16% require FMN, whereas 5 proteins require both.
Flavoproteins are mainly located in the
mitochondria.
Of all flavoproteins, 90% perform redox reactions and the other 10% are
transferases,
lyases
In biochemistry, a lyase is an enzyme that catalyzes the breaking (an elimination reaction) of various chemical bonds by means other than hydrolysis (a substitution reaction) and oxidation, often forming a new double bond or a new ring structure. ...
,
isomerases
Isomerases are a general class of enzymes that convert a molecule from one isomer to another. Isomerases facilitate intramolecular rearrangements in which bonds are broken and formed. The general form of such a reaction is as follows:
A–B ...
,
ligases.
Discovery
Flavoproteins were first mentioned in 1879, when they isolated as a bright-yellow
pigment
A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at some stage in their use. Generally dyes are often organic compounds whereas pigments are often inorganic comp ...
from cow's milk. They were initially termed ''lactochrome''. By the early 1930s, this same pigment had been isolated from a range of sources, and recognised as a component of the
vitamin B complex
B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism and synthesis of red blood cells. Though these vitamins share similar names (B1, B2, B3, etc.), they are chemically distinct compounds that often co ...
. Its structure was determined and reported in 1935 and given the name
riboflavin
Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved in e ...
, derived from the ribityl side chain and yellow colour of the conjugated ring system.
The first evidence for the requirement of flavin as an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
cofactor came in 1935.
Hugo Theorell and coworkers showed that a bright-yellow-coloured
yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to consti ...
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
, identified previously as essential for
cellular respiration
Cellular respiration is the process by which biological fuels are oxidised in the presence of an inorganic electron acceptor such as oxygen to produce large amounts of energy, to drive the bulk production of ATP. Cellular respiration may be des ...
, could be separated into
apoprotein
Apoprotein may refer to:
* Apoenzyme, the protein part of an enzyme without its characteristic prosthetic group
* Apolipoprotein, a lipid-binding protein that is a constituent of the plasma lipoprotein
{{disambiguation ...
and a bright-yellow pigment. Neither apoprotein nor pigment alone could catalyse the
oxidation
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...
of
NADH
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ...
, but mixing of the two restored the enzyme activity. However, replacing the isolated pigment with riboflavin did not restore enzyme activity, despite their being indistinguishable under
spectroscopy
Spectroscopy is the field of study that measures and interprets the electromagnetic spectra that result from the interaction between electromagnetic radiation and matter as a function of the wavelength or frequency of the radiation. Matter ...
. This led to the discovery that the protein studied required not riboflavin but
flavin mononucleotide
Flavin mononucleotide (FMN), or riboflavin-5′-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as the prosthetic group of various oxidoreductases, including NADH dehydrogenase, a ...
to be catalytically active.
Similar experiments with
D-amino acid oxidase
D-amino acid oxidase (DAAO; also OXDA, DAMOX) is an enzyme with the function on a molecular level to oxidize D-amino acids to the corresponding α-keto acids, producing ammonia and hydrogen peroxide. This results in a number of physiologic ...
led to the identification of
flavin adenine dinucleotide
Flavin may refer to:
Placename
* Flavin, Aveyron, a commune in southern France
Surname
* Adrian Flavin (born 1979), a professional rugby player
* Christopher Flavin, president of the Worldwatch Institute
* Dan Flavin (1933–1996), a minimali ...
(FAD) as a second form of flavin utilised by enzymes.
Examples
The flavoprotein family contains a diverse range of enzymes, including:
*
Adrenodoxin reductase that is involved in steroid hormone synthesis in vertebrate species, and has a ubiquitous distribution in metazoa and prokaryotes.
*
Cytochrome P450 reductase that is a redox partner of cytochrome P450 proteins located in endoplasmic reticulum.
*Epidermin
biosynthesis protein, EpiD, which has been shown to be a flavoprotein that
bind
BIND () is a suite of software for interacting with the Domain Name System (DNS). Its most prominent component, named (pronounced ''name-dee'': , short for ''name daemon''), performs both of the main DNS server roles, acting as an authoritative ...
s FMN. This
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
catalyses the removal of two reducing equivalents from the
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, s ...
residue of the C-terminal meso-
lanthionine of epidermin to form a --CC-- double bond.
*The B chain of dipicolinate
synthase In biochemistry, a synthase is an enzyme that catalyses a synthesis process.
Note that, originally, biochemical nomenclature distinguished synthetases and synthases. Under the original definition, synthases do not use energy from nucleoside tripho ...
, an enzyme which
catalyses the formation of
dipicolinic acid from dihydroxydipicolinic acid.
*Phenylacrylic acid decarboxylase , and enzyme which confers resistance to
cinnamic acid
Cinnamic acid is an organic compound with the formula C6H5-CH=CH- COOH. It is a white crystalline compound that is slightly soluble in water, and freely soluble in many organic solvents. Classified as an unsaturated carboxylic acid, it occurs n ...
in
yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to consti ...
See also
*
Phototropin
*
Cryptochrome
Cryptochromes (from the Greek κρυπτός χρώμα, "hidden colour") are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields ...
References
External links
* The menu "science" of the progra
STRAPprovides A comprehensive collection of all flavo-proteins with known 3D-structure. It compares the protein structures to elucidate phylogenetic relationships.
{{InterPro content, IPR003382
Protein families
Proteins