5′-Phosphoribosyl-5-aminoimidazole (or aminoimidazole ribotide, AIR) is a biochemical intermediate in the formation of
purine
Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which includ ...
nucleotides via
inosine-5-monophosphate, and hence is a building block for
DNA and
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
.
The vitamins
thiamine
Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thi ...
and
cobalamin also contain fragments derived from AIR.
It is an intermediate in the
adenine pathway
Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.
Biosynthesis
Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to ri ...
and is synthesized from
5′-phosphoribosylformylglycinamidine by
AIR synthetase
The atmosphere of Earth is the layer of gases, known collectively as air, retained by Earth's gravity that surrounds the planet and forms its planetary atmosphere. The atmosphere of Earth protects life on Earth by creating pressure allowing for ...
.
Chemistry
5-aminoimidazole derivatives were considered unstable and therefore difficult to synthesize. The first non-enzymatic synthesis of 5-aminoimidazole ribotide (AIR) was only published in 1988 and general methodology for other examples was developed in the 1990s.
Biosynthesis
The
furanose
A furanose is a collective term for carbohydrates that have a chemical structure that includes a five-membered ring system consisting of four carbon atoms and one oxygen atom. The name derives from its similarity to the oxygen heterocycle furan, bu ...
(5-
carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent
In chemistry, the valence (US spelling) or valency (British spelling) of an element is the measure of its combining capacity with o ...
)
sugar
Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...
in AIR comes from the
pentose phosphate pathway, which converts
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
(as its
6-phosphate derivative) into
ribose 5-phosphate
Ribose 5-phosphate (R5P) is both a product and an intermediate of the pentose phosphate pathway. The last step of the Redox, oxidative reactions in the pentose phosphate pathway is the production of ribulose 5-phosphate. Depending on the body's s ...
(R5P). The subsequent reactions which attach the
aminoimidazole
Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole Diazole refers ...
portion of the molecule begin when R5P is activated as its
pyrophosphate derivative,
phosphoribosyl pyrophosphate
Phosphoribosyl pyrophosphate (PRPP) is a pentose phosphate. It is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, as well as in pyrimidine nucleotide formation. Hence it is a building block for DNA ...
(PRPP). This reaction is catalysed by
ribose-phosphate diphosphokinase
Ribose-phosphate diphosphokinase (or phosphoribosyl pyrophosphate synthetase or ribose-phosphate pyrophosphokinase) is an enzyme that converts ribose 5-phosphate into phosphoribosyl pyrophosphate (PRPP). It is classified under .
The enzyme is i ...
.
:
Five biosynthetic steps complete the transformation.
[ The first enzyme, ]amidophosphoribosyltransferase
Amidophosphoribosyltransferase (ATase), also known as glutamine phosphoribosylpyrophosphate amidotransferase (GPAT), is an enzyme responsible for catalyzing the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) into 5-phosphoribosyl-1-amine ...
, attaches 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 was ...
from glutamine to the ribotide at its anomeric carbon
In carbohydrate chemistry, a pair of anomers () is a pair of near-identical stereoisomers that differ at only the anomeric carbon, the carbon that bears the aldehyde or ketone functional group in the sugar's open-chain form. However, in order fo ...
, forming phosphoribosylamine
Phosphoribosylamine (PRA) is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. The vitamins thiamine and cobalamin also contain fragments derived from PRA ...
(PRA):
: + → + + PPi
Next, PRA is converted to glycineamide ribonucleotide
Glycineamide ribonucleotide (or GAR) is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. The vitamins thiamine and cobalamin also contain fragments deri ...
(GAR) by the action of phosphoribosylamine—glycine ligase, forming an amide bond with glycine in a process driven by ATP
ATP may refer to:
Companies and organizations
* Association of Tennis Professionals, men's professional tennis governing body
* American Technical Publishers, employee-owned publishing company
* ', a Danish pension
* Armenia Tree Project, non ...
:
: + + ATP → + ADP + Pi
A third enzyme, phosphoribosylglycinamide formyltransferase
Phosphoribosylglycinamide formyltransferase (, ''2-amino-N-ribosylacetamide 5'-phosphate transformylase'', ''GAR formyltransferase'', ''GAR transformylase'', ''glycinamide ribonucleotide transformylase'', ''GAR TFase'', ''5,10-methenyltetrahydrofol ...
, adds a formyl group from 10-formyltetrahydrofolate to GAR, giving phosphoribosyl-N-formylglycineamide
Phosphoribosyl-''N''-formylglycineamide (or FormylGlycinAmideRibotide, FGAR) is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. The vitamins thiamine an ...
(FGAR):
:GAR + 10-formyltetrahydrofolate → FGAR + tetrahydrofolate
The penultimate step converts FGAR to an amidine by the action of phosphoribosylformylglycinamidine synthase
In enzymology, a phosphoribosylformylglycinamidine synthase () is an enzyme that catalyzes the chemical reaction
:ATP + ''N''2-formyl-''N''1-(5-phospho-D-ribosyl)glycinamide + L-glutamine + H2O \rightleftharpoons ADP + phosphate + 2-(formamido)-'' ...
, transferring an amino group from glutamine and giving 5′-phosphoribosylformylglycinamidine (FGAM) in a reaction that also requires ATP:
:FGAR + ATP + glutamine + H2O → FGAM + ADP + glutamate + Pi
FGAM is finally converted to AIR by the action of AIR synthetase
The atmosphere of Earth is the layer of gases, known collectively as air, retained by Earth's gravity that surrounds the planet and forms its planetary atmosphere. The atmosphere of Earth protects life on Earth by creating pressure allowing for ...
which uses ATP to activate the terminal carbonyl group to attack by the nitrogen atom at the anomeric centre:
:FGAM + ATP → AIR + ADP + Pi + H+
:
Use as an intermediate in biosynthesis
Purines
The purine
Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which includ ...
ring system of the nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
inosine monophosphate is formed in a pathway from AIR that begins when phosphoribosylaminoimidazole carboxylase converts it to the carboxylated
Carboxylation is a chemical reaction in which a carboxylic acid is produced by treating a substrate with carbon dioxide. The opposite reaction is decarboxylation. In chemistry, the term carbonation is sometimes used synonymously with carboxylat ...
derivative in the imidazole ring, 5′-phosphoribosyl-4-carboxy-5-aminoimidazole (CAIR).
:AIR + CO2 → CAIR + 2 H+
:
The same compound can be formed in a two-step pathway when the enzymes involved are 5-(carboxyamino)imidazole ribonucleotide synthase and 5-(carboxyamino)imidazole ribonucleotide mutase.
Radical SAM reactions
Rearrangement reactions starting from AIR incorporate portions of the molecule into additional biochemical pathways. The enzymes involved are in the radical SAM superfamily of iron–sulfur protein
Iron–sulfur proteins (or iron–sulphur proteins in British spelling) are proteins characterized by the presence of iron–sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states. Iron–sulfur clu ...
s, which use S-adenosyl methionine
''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...
as a cofactor to initiate the conversions via radical
Radical may refer to:
Politics and ideology Politics
*Radical politics, the political intent of fundamental societal change
*Radicalism (historical), the Radical Movement that began in late 18th century Britain and spread to continental Europe and ...
intermediates.[
]
Thiamine
The vitamin thiamine
Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thi ...
contains a pyrimidine
Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other ...
ring system which is formed from AIR in a reaction catalysed by phosphomethylpyrimidine synthase
Phosphomethylpyrimidine synthase (, ''thiC (gene)'') is an enzyme with List of enzymes, systematic name ''5-amino-1-(5-phospho-D-ribosyl)imidazole formate-lyase (decarboxylating, 4-amino-2-methyl-5-phosphomethylpyrimidine-forming)''. This enzyme ca ...
.[
:
This reaction incorporates the blue, green and red fragments shown into the product, 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate.]
5-Hydroxybenzimidazole
In some anaerobes
An anaerobic organism or anaerobe is any organism that does not require molecular oxygen for growth. It may react negatively or even die if free oxygen is present. In contrast, an aerobic organism (aerobe) is an organism that requires an oxygenate ...
, AIR is a precursor to 5,6-dimethylbenzimidazole, which is incorporated into vitamin B12 in later steps of cobalamin biosynthesis
Cobalamin biosynthesis is the process by which bacteria and archea make Vitamin B12, cobalamin, vitamin B12. Many steps are involved in converting aminolevulinic acid via uroporphyrinogen III and adenosylcobyric acid to the final forms in which it ...
. The initial reaction is catalysed by 5-hydroxybenzimidazole synthase, , and forms 5-hydroxybenzimidazole:
:
All the carbon atoms of the product are transferred from AIR, as shown.[
]
References
{{DEFAULTSORT:Aminoimidazole ribotide, 5-
Nucleotides