AIR synthetase (FGAM cyclase)
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Phosphoribosylformylglycinamidine cyclo-ligase (AIR synthetase) is the fifth
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
() in the ''de novo'' synthesis of
purine Purine is a 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 include substituted purines ...
nucleotides. It catalyzes the reaction to form
5-aminoimidazole ribotide 5′-Phosphoribosyl-5-aminoimidazole (or aminoimidazole ribotide, AIR) 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 coba ...
(AIR) from formylglycinamidine-ribonucleotide FGAM. This reaction closes the ring and produces a 5-membered imidazole ring of the purine nucleus (AIR):
ATP + 2-(formamido)-N1-(5-phospho-β-D-ribosyl)acetamidine \rightleftharpoons ADP + 5-amino-1-(5-phospho-β-D-ribosyl)imidazole + phosphate +
AIR synthetase catalyzes the transfer of the oxygen of the formyl group to phosphate. It is a sequential mechanism in which ATP binds first to the enzyme and ADP is released last. This enzyme hydrolyzes ATP to activate the oxygen of the amide in order to carry out a nucleophilic attack by nitrogen. In humans and many other animals, this enzyme is contained within the trifunctional purine biosynthetic protein adenosine-3 polypeptide.


Nomenclature

The systematic name of this enzyme class is 2-(formamido)-N1-(5-phosphoribosyl)acetamidine cyclo-ligase (ADP-forming). Other names in common use include: * AIR synthetase, * 5'-aminoimidazole ribonucleotide synthetase, * 2-(formamido)-1-N-(5-phosphoribosyl)acetamidine cyclo-ligase (ADP-forming), * phosphoribosylaminoimidazole synthetase, and * phosphoribosylformylglycinamidine cyclo-ligase.


Purine Synthesis

Purines are one of the two types of nitrogenous heterocyclic bases, which are one of the three components of the nucleotides that make up nucleic acids. Synthesis can be de novo or salvage — AIR synthetase is a component of the ''de novo'' pathway. The first committed step of the de novo pathway begins with phosphoribosyl pyrophosphate (PRPP) and the end product is inosine monophosphate (IMP). IMP is eventually converted to either AMP or GMP purines. The purine ring structure is composed by the attachment of 1 or 2 atoms at a time to the ribose sugar. The ''de novo'' pathway tends to be conserved across most organisms.


Cowpea AIR synthetase

AIR synthetase is found in both
mitochondria A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
and
plastid The plastid (Greek: πλαστός; plastós: formed, molded – plural plastids) is a membrane-bound organelle found in the cells of plants, algae, and some other eukaryotic organisms. They are considered to be intracellular endosymbiotic cyan ...
s; the mitochondrial form has 5 more amino acids than the plastid form. The enzyme is encoded by a single gene in cowpeas despite the fact that it exists in different forms in plastids and mitochondria. This suggests that the different versions may be derived from a single transcript. One study proposes that there is tight transcriptional control of pur5, the gene encoding AIR synthetase.


References


Further reading

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External links

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