Deamination
Encyclopedia
Deamination is the removal of an amine
group from a molecule
. Enzyme
s which catalyse
this reaction are called deaminases.
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 if there is an excess of protein intake. 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.
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-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 3'-->5' 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. [See Base excision repair
]
results in thymine
and ammonia. This is the most common single nucleotide mutation. In DNA, this reaction can be corrected by the enzyme thymine DNA glycosylase (J. Biol. Chem. 271:12767-12774(1996)) prior to passage of the replication fork, which would fix the cytosine to thymine point mutation in one of the two daughter strands.
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.
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.
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
group from a molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
. Enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s which catalyse
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
this reaction are called deaminases.
In the human body
Human body
The human body is the entire structure of a human organism, and consists of a head, neck, torso, two arms and two legs.By the time the human reaches adulthood, the body consists of close to 100 trillion cells, the basic unit of life...
, deamination takes place primarily in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, however glutamate is also deaminated in the kidneys. Deamination is the process by which amino acids are broken down if there is an excess of protein intake. The amino group is removed from the amino acid and converted to ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
. The rest of the amino acid is made up of mostly carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
and hydrogen
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...
, and is recycled or oxidized for energy. Ammonia is toxic to the human system, and enzymes convert it to urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
or uric acid
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 created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
by addition of carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
molecules (which is not considered a deamination process) in the urea cycle
Urea cycle
The urea cycle is a cycle of biochemical reactions occurring in many animals that produces urea from ammonia . This cycle was the first metabolic cycle discovered , five years before the discovery of the TCA cycle...
, which also takes place in the liver. Urea and uric acid can safely diffuse into the blood and then be excreted in urine.
Cytosine
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
reaction of cytosine
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...
into uracil
Uracil
Uracil is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine, cytosine, and guanine. In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine.Uracil is a common and...
, releasing ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
in the process. This can occur in vitro through the use of bisulfite
Bisulfite
Bisulfite ion is the ion HSO3−. Salts containing the HSO3− ion are termed bisulfites also known as sulfite lyes...
, which converts cytosine, but not 5-methylcytosine
5-Methylcytosine
5-Methylcytosine is a methylated form of the DNA base cytosine that may be involved in the regulation of gene transcription. When cytosine is methylated, the DNA maintains the same sequence, but the expression of methylated genes can be altered .In the figure on the right, a methyl group, is...
. This property has allowed researchers to sequence
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
methylated DNA to distinguish non-methylated cytosine (shown up as uracil
Uracil
Uracil is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine, cytosine, and guanine. In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine.Uracil is a common and...
) and methylated cytosine (unaltered).
In DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, 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
Uracil-DNA glycosylase, also known as UNG or UDG, is a human gene though orthologs exist ubiquitously among prokaryotes and eukaryotes and even in some DNA viruses. The first uracil DNA-glycosylase was isolated from Escherichia coli....
, 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
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
may perform this replacement via nick translation
Nick translation
Nick translation was developed in 1977 by Rigby and Paul Berg. It 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 analogues, creating a tagged DNA sequence which can be used as a probe in...
, a terminal excision reaction by its 3'-->5' 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. [See Base excision repair
Base excision repair
In biochemistry and genetics, base excision repair is a cellular mechanism that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky...
]
5-methylcytosine
Spontaneous deamination of 5-methylcytosine5-Methylcytosine
5-Methylcytosine is a methylated form of the DNA base cytosine that may be involved in the regulation of gene transcription. When cytosine is methylated, the DNA maintains the same sequence, but the expression of methylated genes can be altered .In the figure on the right, a methyl group, is...
results in thymine
Thymine
Thymine 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 pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...
and ammonia. This is the most common single nucleotide mutation. In DNA, this reaction can be corrected by the enzyme thymine DNA glycosylase (J. Biol. Chem. 271:12767-12774(1996)) prior to passage of the replication fork, which would fix the cytosine to thymine point mutation in one of the two daughter strands.
Guanine
Deamination of guanineGuanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
results in the formation of xanthine. Xanthine, in a manner analogous to the enol tautomer of guanine, selectively base pairs with thymine
Thymine
Thymine 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 pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...
instead of cytosine
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...
. 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 adenineAdenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
results in the formation of hypoxanthine. Hypoxanthine, in a manner analogous to the imine tautomer of adenine, selectively base pairs with cytosine
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...
instead of thymine
Thymine
Thymine 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 pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...
. This results in a post-replicative transition mutation, where the original A-T base pair transforms into a G-C base pair.