Editing Deamination

{{Short description|Removal of an amino group from a molecule}}
{{More citations needed|date=March 2014}}
{{About-distinguish2|enzymatic processes|[[nitrosation#Of amines|nitrosation]]}}
'''Deamination''' is the removal of an [[amino group]] from a [[molecule]].<ref>{{citation | author = Smith, Michael B. | author2 = March, Jerry | author2-link = Jerry March | date = 2013 | title = Advanced Organic Chemistry: Reactions, Mechanisms, and Structure | edition = 7th | location = New York | publisher = Wiley-Interscience | page = 1547 }}</ref> [[Enzyme]]s that [[catalysis|catalyse]] this reaction are called '''deaminases'''.

In the [[human body]], deamination takes place primarily in the [[liver]]; however, it can also occur in the [[kidney]]. 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]]. The rest of the amino acid is made up of mostly [[carbon]] and [[hydrogen]], and is recycled or oxidized for energy. Ammonia is toxic to the human system, and [[enzymes]] convert it to [[urea]] or [[uric acid]] by addition of [[carbon dioxide]] molecules (which is not considered a deamination process) in 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===
{{Plain image with caption|DesaminierungCtoU.png|Deamination of [[cytosine]] to [[uracil]].|275px|right|bottom|triangle|grey}}
Spontaneous deamination is the [[hydrolysis]] reaction of [[cytosine]] into [[uracil]], releasing [[ammonia]] in the process. This can occur in vitro through the use of [[bisulfite]], which deaminates cytosine, but not [[5-methylcytosine]]. This property has allowed researchers to [[DNA sequencing|sequence]] [[DNA methylation|methylated]] DNA to distinguish non-methylated cytosine (shown up as [[uracil]]) 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]], generating an abasic (AP) site. The resulting [[abasic site]] is then recognised by enzymes ([[AP endonuclease]]s) that break a phosphodiester bond in the DNA, permitting the repair of the resulting lesion by replacement with another cytosine. A [[DNA polymerase]] may perform this replacement via [[nick translation]], 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]]).

===5-methylcytosine===
Spontaneous deamination of [[5-methylcytosine]] results in [[thymine]] 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.<ref>{{Cite journal |doi= 10.1074/jbc.271.22.12767 |title= Cloning and Expression of Human G/T Mismatch-specific Thymine-DNA Glycosylase |journal= Journal of Biological Chemistry |volume= 271 |issue= 22 |pages= 12767–74 |year= 1996 |last1= Gallinari |first1= P. |pmid=8662714|doi-access= free }}</ref>

==== 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]]s (TEs) may become transcriptionally active due to the loss of CPG sites.<ref name=":0">{{Cite journal|last1=Zhou|first1=Wanding|last2=Liang|first2=Gangning|last3=Molloy|first3=Peter L.|last4=Jones|first4=Peter A.|date=11 August 2020|title=DNA methylation enables transposable element-driven genome expansion|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=117|issue=32|pages=19359–19366|doi=10.1073/pnas.1921719117|issn=1091-6490|pmc=7431005|pmid=32719115|bibcode=2020PNAS..11719359Z |doi-access=free }}</ref> 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.<ref name=":0" />

===Guanine===
Deamination of [[guanine]] results in the formation of [[xanthine]]. Xanthine, however, still pairs with [[cytosine]].<ref>Tyagi, R. (2009). Understanding Genetics and Evolution: Discovery Publishing House.</ref><ref>Herriott, R. M. (1966). Mutagenesis. Cancer Research, 26(9 Part 1)</ref>

===Adenine===
Deamination of [[adenine]] results in the formation of [[hypoxanthine]]. Hypoxanthine, in a manner analogous to the imine tautomer of adenine, selectively base pairs with [[cytosine]] instead of [[thymine]]. 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]]
*[[Activation-induced cytidine deaminase]] (AICDA)
*[[Cytidine deaminase]] (CDA)
*[[dCMP deaminase]] (DCTD)
*[[AMP deaminase]] (AMPD1)
*Adenosine Deaminase acting on tRNA (ADAT)
*Adenosine Deaminase acting on dsRNA ([[ADAR]])
**Double-stranded RNA-specific editase 1 ([[ADARB1]])
*Adenosine Deaminase acting on mononucleotides (ADA)
*Guanine Deaminase (GDA)

== See also ==
* [[Adenosine monophosphate deaminase deficiency type 1]]
* [[Hofmann elimination]]

==References==
{{reflist}}

[[Category:Biochemical reactions]]
[[Category:Metabolism]]
[[Category:Substitution reactions]]