Deamination is the removal of an

amino group In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

from a

molecule A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

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 ...

s that

catalyse Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

this reaction are called deaminases. In the

human body The human body is the entire structure of a Human, human being. It is composed of many different types of Cell (biology), cells that together create Tissue (biology), tissues and subsequently Organ (biology), organs and then Organ system, org ...

, deamination takes place primarily in the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

; however, it can also occur in the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

. In situations of excess protein intake, deamination is used to break down

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

for energy. The amino group is removed from the amino acid and converted to

ammonia Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...

. The rest of the amino acid is made up of mostly

carbon Carbon () is a chemical element; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...

and

hydrogen Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...

, and is recycled or oxidized for energy. Ammonia is toxic to the human system, and

enzymes An enzyme () is a protein that acts as a biological catalyst 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 pro ...

convert it to

urea Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...

uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the Chemical formula, formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the meta ...

by addition of

carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...

molecules (which is not considered a deamination process) in the

urea cycle The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic. The urea cycle converts highl ...

, which also takes place in the liver. Urea and uric acid can safely diffuse into the blood and then be excreted in urine.

Deamination reactions in DNA

Cytosine

Spontaneous deamination is the

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

reaction of

cytosine Cytosine () (symbol C or Cyt) is one of the four nucleotide bases found in DNA and RNA, along with adenine, guanine, and thymine ( uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attac ...

into

uracil Uracil () (nucleoside#List of nucleosides and corresponding nucleobases, symbol U or Ura) is one of the four nucleotide bases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via ...

, releasing

in the process. This can occur in vitro through the use of

bisulfite The bisulfite ion (IUPAC-recommended nomenclature: hydrogensulfite) is the ion . Salts containing the ion are also known as "sulfite lyes". Sodium bisulfite is used interchangeably with sodium metabisulfite (Na2S2O5). Sodium metabisulfite diss ...

, which deaminates cytosine, but not

5-methylcytosine 5-Methylcytosine (5mC) is a methylation, methylated form of the DNA base cytosine (C) that regulates gene Transcription (genetics), transcription and takes several other biological roles. When cytosine is methylated, the DNA maintains the same s ...

. This property has allowed researchers to

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is cal ...

methylated Methylation, in the chemical sciences, is the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These term ...

DNA to distinguish non-methylated cytosine (shown up as

) and methylated cytosine (unaltered). In

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

, this spontaneous deamination is corrected for by the removal of uracil (product of cytosine deamination and ''not'' part of DNA) by

uracil-DNA glycosylase Uracil-DNA glycosylase (also known as UNG or UDG) is an enzyme. Its most important function is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosidic bond and initiating the base-excision repair (BER) pathway ...

, generating an abasic (AP) site. The resulting abasic site is then recognised by enzymes (

AP endonuclease Apurinic/apyrimidinic (AP) endonuclease is an enzyme that is involved in the DNA base excision repair pathway (BER). Its main role in the repair of damaged or mismatched nucleotides in DNA is to create a nick in the phosphodiester backbone of t ...

s) that break a phosphodiester bond in the DNA, permitting the repair of the resulting lesion by replacement with another cytosine. A

DNA polymerase A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create t ...

may perform this replacement via

nick translation Nick translation (or head translation), developed in 1977 by Peter Rigby and Paul Berg, is a tagging technique in molecular biology in which DNA polymerase I is used to replace some of the nucleotides of a DNA sequence with their labeled analogue ...

, a terminal excision reaction by its 5'⟶3' exonuclease activity, followed by a fill-in reaction by its polymerase activity. DNA ligase then forms a phosphodiester bond to seal the resulting nicked duplex product, which now includes a new, correct cytosine (

Base excision repair Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from t ...

5-methylcytosine

Spontaneous deamination of

results in

thymine Thymine () (symbol T or Thy) is one of the four nucleotide bases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine ...

and ammonia. This is the most common single nucleotide mutation. In DNA, this reaction, if detected prior to passage of the replication fork, can be corrected by the enzyme thymine-DNA glycosylase, which removes the thymine base in a G/T mismatch. This leaves an abasic site that is repaired by AP endonucleases and polymerase, as with uracil-DNA glycosylase.

Cytosine deamination increases C-To-T mutations

A known result of cytosine methylation is the increase of C-to-T transition mutations through the process of deamination. Cytosine deamination can alter the genome's many regulatory functions; previously silenced

transposable element A transposable element (TE), also transposon, or jumping gene, is a type of mobile genetic element, a nucleic acid sequence in DNA that can change its position within a genome. The discovery of mobile genetic elements earned Barbara McClinto ...

s (TEs) may become transcriptionally active due to the loss of CPG sites. TEs have been proposed to accelerate the mechanism of enhancer creation by providing extra DNA that is compatible with the host transcription factors that eventually have an impact on C-to-T mutations.

Guanine

Deamination of

guanine Guanine () (symbol G or Gua) is one of the four main nucleotide bases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside ...

results in the formation of

xanthine Xanthine ( or , from Ancient Greek for its yellowish-white appearance; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms. Several ...

. Xanthine, however, still pairs with

.Herriott, R. M. (1966). Mutagenesis. Cancer Research, 26(9 Part 1)

Adenine

Deamination of

adenine Adenine (, ) (nucleoside#List of nucleosides and corresponding nucleobases, symbol A or Ade) is a purine nucleotide base that is found in DNA, RNA, and Adenosine triphosphate, ATP. Usually a white crystalline subtance. The shape of adenine is ...

results in the formation of

hypoxanthine Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids, where it is present in the anticodon of tRNA in the form of its nucleoside inosine. It has a tautomer known as 6-hydroxypurine. Hyp ...

. Hypoxanthine, in a manner analogous to the imine tautomer of adenine, selectively base pairs with

instead of

. This results in a post-replicative transition mutation, where the original A-T base pair transforms into a G-C base pair.

Additional proteins performing this function

*APOBEC1 *APOBEC3A-H, APOBEC3G - affects

HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...

* Activation-induced cytidine deaminase (AICDA) * Cytidine deaminase (CDA) *

dCMP deaminase dCMP deaminase (, ''deoxycytidylate deaminase'', ''deoxy-CMP-deaminase'', ''deoxycytidylate aminohydrolase'', ''deoxycytidine monophosphate deaminase'', ''deoxycytidine-5'-phosphate deaminase'', ''deoxycytidine-5'-monophosphate aminohydrolase'') ...

(DCTD) * AMP deaminase (AMPD1) *Adenosine Deaminase acting on tRNA (ADAT) *Adenosine Deaminase acting on dsRNA (

ADAR Adar (Hebrew: , ; from Akkadian ''adaru'') is the sixth month of the civil year and the twelfth month of the religious year on the Hebrew calendar, roughly corresponding to the month of March in the Gregorian calendar. It is a month of 29 days. ...

) **Double-stranded RNA-specific editase 1 ( ADARB1) *Adenosine Deaminase acting on mononucleotides (ADA) *Guanine Deaminase (GDA)

References

{{reflist Biochemical reactions Metabolism Substitution reactions