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, re ...
that contain a
nucleic acid
Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a pentose, 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nuclei ...
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 ...
. These proteins are involved in a wide array of biological processes, including removal of
radicals contributing to oxidative stress,
photosynthesis
Photosynthesis ( ) is a system of biological processes by which photosynthetic organisms, such as most plants, algae, and cyanobacteria, convert light energy, typically from sunlight, into the chemical energy necessary to fuel their metabo ...
, and
DNA repair. The flavoproteins are some of the most-studied families of enzymes.
Flavoproteins have either FMN (
flavin mononucleotide) or FAD (
flavin adenine dinucleotide) 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,
isomerases,
ligases.
Discovery
Flavoproteins were first mentioned in 1879, when they isolated as a bright-yellow
pigment
A pigment is a powder used to add or alter color or change visual appearance. Pigments are completely or nearly solubility, insoluble and reactivity (chemistry), chemically unreactive in water or another medium; in contrast, dyes are colored sub ...
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. 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 ...
, 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
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 ...
cofactor came in 1935.
Hugo Theorell and coworkers showed that a bright-yellow-coloured
yeast protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
, identified previously as essential for
cellular respiration
Cellular respiration is the process of oxidizing biological fuels using an inorganic electron acceptor, such as oxygen, to drive production of adenosine triphosphate (ATP), which stores chemical energy in a biologically accessible form. Cell ...
, could be separated into
apoprotein and a bright-yellow pigment. Neither apoprotein nor pigment alone could catalyse the
oxidation
Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...
of
NADH, but mixing of the two restored the enzyme activity. However, replacing the isolated pigment with riboflavin did not restore enzyme activity, despite being indistinguishable under
spectroscopy
Spectroscopy is the field of study that measures and interprets electromagnetic spectra. In narrower contexts, spectroscopy is the precise study of color as generalized from visible light to all bands of the electromagnetic spectrum.
Spectro ...
. This led to the discovery that the protein studied required not riboflavin but
flavin mononucleotide to be catalytically active.
Similar experiments with
D-amino acid oxidase led to the identification of
flavin adenine dinucleotide (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
Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...
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 (computing), daemon''), performs both of the main DNS server roles, acting ...
s FMN. This
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 ...
catalyses the removal of two reducing equivalents from the
cysteine residue of the C-terminal ''meso''-
lanthionine of epidermin to form a --CC-- double bond
* The B chain of
dipicolinate synthase, an enzyme which
catalyses the formation of
dipicolinic acid from dihydroxydipicolinic acid
*
Phenylacrylic acid decarboxylase (), an enzyme which confers resistance to
cinnamic acid in
yeast
*
Phototropin and
cryptochrome, light-sensing proteins
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