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 DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...

. The flavoproteins are some of the most-studied families of enzymes. Flavoproteins have either FMN (

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 ...

) or FAD (

flavin adenine dinucleotide In biochemistry, flavin adenine dinucleotide (FAD) is a redox-active coenzyme associated with various proteins, which is involved with several enzymatic reactions in metabolism. A flavoprotein is a protein that contains a flavin group, which ma ...

) 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 A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

. Of all flavoproteins, 90% perform redox reactions and the other 10% are

transferases In biochemistry, a transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl group, methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They ...

, 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

, 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 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 Ka ...

and coworkers showed that a bright-yellow-coloured

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...

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 ...

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 ade ...

, 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

to be catalytically active. Similar experiments with D-amino acid oxidase led to the identification of

(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

catalyses the removal of two reducing equivalents from the

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

residue of the C-terminal ''meso''- lanthionine of epidermin to form a --C

C-- 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 Cinnamic acid is an organic compound with the formula phenyl, C6H5-CH=CH-Carboxylic acid, COOH. It is a white crystalline compound that is slightly soluble in water, and freely soluble in many organic solvents. Classified as an unsaturated carboxy ...

* Phototropin and

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 fiel ...

, light-sensing proteins

References

External links

* The menu "science" of the progra
STRAP
provides 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