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Deamination

Deamination is the removal of an amino group from a molecule.[1] Enzymes that 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 edit

Cytosine edit

 
Deamination of cytosine to uracil.

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 sequence 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 endonucleases) 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 edit

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.[2]

Cytosine deamination increases C-To-T mutations edit

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 elements (TEs) may become transcriptionally active due to the loss of CPG sites.[3] 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.[3]

Guanine edit

Deamination of guanine results in the formation of xanthine. Xanthine, however, still pairs with cytosine.[4][5]

Adenine edit

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 edit

See also edit

References edit

  1. ^ Smith, Michael B.; March, Jerry (2013), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (7th ed.), New York: Wiley-Interscience, p. 1547
  2. ^ Gallinari, P. (1996). "Cloning and Expression of Human G/T Mismatch-specific Thymine-DNA Glycosylase". Journal of Biological Chemistry. 271 (22): 12767–74. doi:10.1074/jbc.271.22.12767. PMID 8662714.
  3. ^ a b Zhou, Wanding; Liang, Gangning; Molloy, Peter L.; Jones, Peter A. (11 August 2020). "DNA methylation enables transposable element-driven genome expansion". Proceedings of the National Academy of Sciences of the United States of America. 117 (32): 19359–19366. Bibcode:2020PNAS..11719359Z. doi:10.1073/pnas.1921719117. ISSN 1091-6490. PMC 7431005. PMID 32719115.
  4. ^ Tyagi, R. (2009). Understanding Genetics and Evolution: Discovery Publishing House.
  5. ^ Herriott, R. M. (1966). Mutagenesis. Cancer Research, 26(9 Part 1)

deamination, this, article, needs, additional, citations, verification, please, help, improve, this, article, adding, citations, reliable, sources, unsourced, material, challenged, removed, find, sources, news, newspapers, books, scholar, jstor, march, 2014, l. This article needs additional citations for verification Please help improve this article by adding citations to reliable sources Unsourced material may be challenged and removed Find sources Deamination news newspapers books scholar JSTOR March 2014 Learn how and when to remove this template message Deamination is the removal of an amino group from a molecule 1 Enzymes that 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 Contents 1 Deamination reactions in DNA 1 1 Cytosine 1 2 5 methylcytosine 1 2 1 Cytosine deamination increases C To T mutations 1 3 Guanine 1 4 Adenine 2 Additional proteins performing this function 3 See also 4 ReferencesDeamination reactions in DNA editCytosine edit nbsp Deamination of cytosine to uracil 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 sequence 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 endonucleases 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 edit 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 2 Cytosine deamination increases C To T mutations edit 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 elements TEs may become transcriptionally active due to the loss of CPG sites 3 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 3 Guanine edit Deamination of guanine results in the formation of xanthine Xanthine however still pairs with cytosine 4 5 Adenine edit 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 editAPOBEC1 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 editAdenosine monophosphate deaminase deficiency type 1 Hofmann eliminationReferences edit Smith Michael B March Jerry 2013 Advanced Organic Chemistry Reactions Mechanisms and Structure 7th ed New York Wiley Interscience p 1547 Gallinari P 1996 Cloning and Expression of Human G T Mismatch specific Thymine DNA Glycosylase Journal of Biological Chemistry 271 22 12767 74 doi 10 1074 jbc 271 22 12767 PMID 8662714 a b Zhou Wanding Liang Gangning Molloy Peter L Jones Peter A 11 August 2020 DNA methylation enables transposable element driven genome expansion Proceedings of the National Academy of Sciences of the United States of America 117 32 19359 19366 Bibcode 2020PNAS 11719359Z doi 10 1073 pnas 1921719117 ISSN 1091 6490 PMC 7431005 PMID 32719115 Tyagi R 2009 Understanding Genetics and Evolution Discovery Publishing House Herriott R M 1966 Mutagenesis Cancer Research 26 9 Part 1 Retrieved from https en wikipedia org w index php title Deamination amp oldid 1157164395, wikipedia, wiki, book, books, library,

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