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
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) as a prosthetic group or as a
cofactor. The flavin is generally tightly bound (as in
adrenodoxin reductase
Adrenodoxin reductase (Enzyme Nomenclature name: adrenodoxin-NADP+ reductase, EC 1.18.1.6), was first isolated from bovine adrenal cortex where it functions as the first enzyme in the mitochondrial P450 systems that catalyze essential steps in st ...
, 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
A transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved in hundreds of d ...
,
lyases,
isomerases,
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 compou ...
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, 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 substrates, and the enzyme converts the substrates into different molecules known as products ...
cofactor came in 1935.
Hugo Theorell
Axel Hugo Theodor Theorell (6 July 1903 – 15 August 1982) was a Swedish scientist and Nobel Prize laureate in medicine.
He was born in Linköping as the son of Thure Theorell and his wife Armida Bill. Theorell went to Secondary School at Kat ...
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 constit ...
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, res ...
, 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 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. 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, as we ...
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
Adrenodoxin reductase (Enzyme Nomenclature name: adrenodoxin-NADP+ reductase, EC 1.18.1.6), was first isolated from bovine adrenal cortex where it functions as the first enzyme in the mitochondrial P450 systems that catalyze essential steps in st ...
that is involved in steroid hormone synthesis in vertebrate species, and has a ubiquitous distribution in metazoa and prokaryotes.
*
Cytochrome P450 reductase
Cytochrome P450 reductase (; also known as NADPH:ferrihemoprotein oxidoreductase, NADPH:hemoprotein oxidoreductase, NADPH:P450 oxidoreductase, P450 reductase, POR, CPR, CYPOR) is a membrane-bound enzyme required for electron transfer from NADP ...
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 substrates, and the enzyme converts the substrates into different molecules known as products ...
catalyses the removal of two reducing equivalents from the
cysteine residue
Residue may refer to:
Chemistry and biology
* An amino acid, within a peptide chain
* Crop residue, materials left after agricultural processes
* Pesticide residue, refers to the pesticides that may remain on or in food after they are applied ...
of the C-terminal meso-
lanthionine
Lanthionine is a nonproteinogenic amino acid with the chemical formula (HOOC-CH(NH2)-CH2-S-CH2-CH(NH2)-COOH). It is typically formed by a cysteine residue and a dehydrated serine residue. Despite its name, lanthionine does not contain the element ...
of epidermin to form a --CC-- double bond.
*The B chain of dipicolinate
synthase, an enzyme which
catalyses the formation of
dipicolinic acid
Dipicolinic acid (pyridine-2,6-dicarboxylic acid or PDC and DPA) is a chemical compound which plays a role in the heat resistance of bacterial endospores. It is also used to prepare dipicolinato ligated lanthanide and transition metal complexes ...
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 na ...
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 constit ...
See also
*
Phototropin
Phototropins are photoreceptor proteins (more specifically, flavoproteins) that mediate phototropism responses in higher plants. Phototropins can be found throughout the leaves of a plant. Along with cryptochromes and phytochromes they allow plants ...
*
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