Deamination is the removal of an
amino group
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...
from a
molecule
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...
.
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 ...
s that
catalyse
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
this reaction are called deaminases.
In the
human body, deamination takes place primarily in the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
, however it can also occur in the
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
. In situations of excess protein intake, deamination is used to break down
amino acids for energy. The amino group is removed from the amino acid and converted to
ammonia
Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous wa ...
. The rest of the amino acid is made up of mostly
carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon mak ...
and
hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic ...
, and is recycled or oxidized for energy. Ammonia is toxic to the human system, and
enzymes convert it to
urea
Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid.
Urea serves an important ...
or
uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the 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 metabolic breakdown ...
by addition of
carbon dioxide
Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...
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 Biochemistry, 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 ...
, 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, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolys ...
reaction of
cytosine
Cytosine () ( symbol C or Cyt) is one of the four nucleobases 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 attached (an ...
into
uracil
Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced b ...
, releasing
ammonia
Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous wa ...
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 disso ...
, which deaminates cytosine, but not
5-methylcytosine. 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 calle ...
methylated
In the chemical sciences, methylation denotes 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 ...
DNA to distinguish non-methylated cytosine (shown up as
uracil
Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced b ...
) and methylated cytosine (unaltered).
In
DNA, 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 is also known as UNG or UDG. 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.
Function
...
, generating an abasic (AP) site. The resulting
abasic site
In biochemistry and molecular genetics, an AP site (apurinic/apyrimidinic site), also known as an abasic site, is a location in DNA (also in RNA but much less likely) that has neither a purine nor a pyrimidine base, either spontaneously or ...
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 ...
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 analogu ...
, 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
5-methylcytosine results in
thymine
Thymine () ( symbol T or Thy) is one of the four nucleobases 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 pyrimidi ...
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
G/T mismatch-specific thymine DNA glycosylase is an enzyme that in humans is encoded by the TDG gene. Several bacterial proteins have strong sequence homology with this protein.
Function
The protein encoded by this gene belongs to the TDG/mug ...
, 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, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transp ...
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 nucleobases 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 is c ...
results in the formation of
xanthine
Xanthine ( or ; 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 stimulants are derived from xanthine, including caffeine ...
. Xanthine, however, still pairs with
cytosine
Cytosine () ( symbol C or Cyt) is one of the four nucleobases 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 attached (an ...
.
[Herriott, R. M. (1966). Mutagenesis. Cancer Research, 26(9 Part 1)]
Adenine
Deamination of
adenine
Adenine () ( symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its deri ...
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. ...
. Hypoxanthine, in a manner analogous to the imine tautomer of adenine, selectively base pairs with
cytosine
Cytosine () ( symbol C or Cyt) is one of the four nucleobases 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 attached (an ...
instead of
thymine
Thymine () ( symbol T or Thy) is one of the four nucleobases 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 pyrimidi ...
. 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
APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic subunit 3G) is a human enzyme encoded by the ''APOBEC3G'' gene that belongs to the APOBEC superfamily of proteins. This family of proteins has been suggested to play an important role in ...
- 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 immune ...
*
Activation-induced cytidine deaminase
Activation-induced cytidine deaminase, also known as AICDA, AID and single-stranded DNA cytosine deaminase, is a 24 kDa enzyme which in humans is encoded by the ''AICDA'' gene. It creates mutations in DNA by deamination of cytosine base, which t ...
(AICDA)
*
Cytidine deaminase
Cytidine deaminase is an enzyme that in humans is encoded by the ''CDA'' gene.
This gene encodes an enzyme involved in pyrimidine salvaging. The encoded protein forms a homotetramer that catalyzes the irreversible hydrolytic deamination of cytid ...
(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
AMP deaminase 1 is an enzyme that in humans is encoded by the ''AMPD1'' gene.
Adenosine monophosphate deaminase is an enzyme that converts adenosine monophosphate (AMP) to inosine monophosphate (IMP), freeing an ammonia molecule in the process.
...
(AMPD1)
*Adenosine Deaminase acting on tRNA (ADAT)
*Adenosine Deaminase acting on dsRNA (
ADAR)
**Double-stranded RNA-specific editase 1 (
ADARB1
Double-stranded RNA-specific editase 1 is an enzyme that in humans is encoded by the ''ADARB1'' gene. The enzyme is a member of ADAR family.
Function
This gene encodes the enzyme responsible for pre-mRNA editing of the glutamate receptor su ...
)
*Adenosine Deaminase acting on mononucleotides (ADA)
*Guanine Deaminase (GDA)
See also
*
Adenosine monophosphate deaminase deficiency type 1
*
Hofmann elimination
Hofmann elimination is an elimination reaction of an amine to form alkenes. The least stable alkene (the one with the least number of substituents on the carbons of the double bond), called the Hofmann product, is formed. This tendency, known as ...
References
{{reflist
Metabolism
Substitution reactions