deaminize

Deamination is the removal of an amine group from a molecule.

In the human body, deamination takes place primarily in the liver, however Glutamate is also deaminated in the kidneys. Deamination is the process by which amino acids are broken down when too much protein has been taken in. 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

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 converts 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 glycosidase, generating an abasic (AP) site. The resulting abasic site is then recognised by enzymes, AP endonucleases) which cut the DNA and allow DNA to repair the lesion by replacement with another cytosine.

5-methylcytosine

Spontaneous deamination of 5-methylcytosine results in thymine and ammonia. This is the most common single nucleotide mutation. In DNA, this reaction cannot be corrected because the repair mechanisms do not recognize thymine as erroneous (as opposed to uracil), and, unless it affects the function of the gene, the mutation will persist. This flaw in the repair mechanism contributes to the rarity of CpG sites in the eukaryotic genome.

Guanine

Deamination of guanine results in the formation of xanthine. Xanthine, in a manner analogous to the enol tautomer of guanine, selectively base pairs with thymine instead of cytosine. This results in a post-replicative transition mutation, where the original G-C base pair transforms into an A-T base pair. Correction of this mutation involves the use of alkyladenine glycosylase during base excision repair.

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

• APOBEC3G - affects HIV

Apolipoprotein B