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Pathway Description
Purine Metabolism
Arabidopsis thaliana
Metabolic Pathway
Purines are heterocyclic aromatic organic compounds that each consist of a pyrimidine ring fused to an imidazole ring. Common in nature, these water-soluble nitrogenous bases can form deoxyribonucleotides (as deoxyadenosine or deoxyguanosine) or ribonucleotides (as adenosine (AMP) or guanosine (GMP)), which are respectively the building blocks of DNA and RNA, both of which are formed by approximately equal amounts of purines and pyrimidines in most eukaryotes. Notable purines include adenine, guanine, caffeine, xanthine, and uric acid. In Arabidopsis thaliana (thale cress), purine metabolism consists of eighteen main key reactions that lead to nucleoside/nucleotide formation, all with well-characterized enzymatic catalysts, although this pathway includes more reactions in order to link purine metabolism to other cellular pathways, such as the pentose phosphate pathway; alanine, aspartate, and glutamate metabolism; thiamine metabolism; histidine metabolism; arginine biosynthesis; folate biosynthesis; riboflavin metabolism; glycine, serine, and threonine metabolism; urate degradation to glyoxylate, and its metabolism. In the chloroplast, adenosine diphosphate ribose is converted to D-ribose 5-phosphate in a reaction catalysed by a chloroplastic hydrolase, after which chloroplastic ribose-phosphate pyrophosphokinase 2 (also known as phosphoribosyl pyrophosphate synthase 2, or PRS II) catalyses the formation of phosphoribosyl pyrophosphate in the chloroplast stroma, which then reacts to form 5-phosphoribosylamine. GAR synthetase, a ligase, then catalyses the formation of 5’-phosphoribosylglycinamide (GAR). 5,10-Methenyltetrahydrofolate and GAR feed into IMP biosynthesis via de novo pathway, beginning with a reaction catalysed by a formyltransferase. In mitochondria or chloroplasts, a probable synthase catalyses the next reaction. Essential to the male gametophyte development, phosphoribosylformylglycinamidine synthase catalyses the ATP-dependent conversion of formylglycinamide ribonucleotide (FGAR) and glutamine to yield formylglycine amidine ribonucleotide (FGAM) and glutamate in the purine biosynthetic pathway. Subsequently, FGAM is converted into aminoimidazole ribotide (AIR) in a reaction catalysed by an ATP- and copper ion-dependent cyclo-ligase. AIR, catalysed by a carboxylase, then forms 1-(5-phospho-D-ribosyl)-5-amino-4-imidazole carboxylate (CAIR), which can form 1-(5’-phosphoribosyl)-5-amino-4-(N-succinocarboxamide)-imidazole (SAICAR) in a reaction catalysed by a chlorolastic synthase. SAICAR can feed into de novo AMP biosynthesis. The next reaction can take place in the cytosol (isoform 2) or in the chloroplast (isoform 1), depending on which protein is expressed. This pathway shows adenine phosphoribosyltransferase isoform 1 (chloroplastic), which catalyzes a salvage reaction resulting in the formation of AMP that is energetically less costly than de novo synthesis. It contributes primarily to the recycling of adenine into adenylate nucleotides, but is also involved in the inactivation of cytokinins by phosphoribosylation and also catalyzes the conversion of cytokinins from free bases (active form) to the corresponding nucleotides (inactive form). The subsequent few reactions take place in the cytosol, leading to the formation of various nucleotides, such as GMP. and indirect cGMP cycling. The nucleoside-diphosphate kinase (which exists in peroxisomes, nuclei, and the cytosol) plays a major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. This enzyme has a role in response to reactive oxygen species (ROS) stress. This reaction is bidirectional, but certain pyrophosphatases may act in one direction to catalyse similar reactions (not shown). Another pyrophosphatase hydrolyzes non-canonical purine nucleotides such as inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) or xanthosine 5’-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms, probably excluding non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions. A cytosolic GDP reductase provides the precursors necessary for DNA synthesis and catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R1 contains the binding sites for both substrates and allosteric effectors and carries out the actual reduction of the ribonucleotide. Ribonucleotide reductase (RNR) complex function is essential for efficient organellar DNA degradation in pollen. It is involved in chloroplast division. Xanthine is formed via a phosphoribosyltransferase-catalysed reaction. Upon NADH oxidase activity via xanthine dehydrogenase, xanthine can react to form uric acid. This enzyme is key to purine catabolism; it catalyses the oxidation of hypoxanthine to xanthine and the oxidation of xanthine to urate in order to regulate the level of ureides and as such, it plays an important role during plant growth and development, senescence and response to stresses. Due to its cofactors, it may contribute to the generation of superoxide anions in planta. Urate oxidase, in the peroxisome, catalyses the oxidation of uric acid to 5-hydroxyisourate, which is further processed to form (S)-allantoin, while (R)-allantoin can form spontaneously. Allantoin, also known as glyoxyldiureide or 5-ureidohydantoin, belongs to the class of organic compounds known as imidazoles. Imidazoles are compounds containing an imidazole ring, which is an aromatic five-member ring with two nitrogen atoms at positions 1 and 3, and three carbon atoms. Allantoin exists as a solid, slightly soluble (in water), and a very weakly acidic compound (based on its pKa). Within the cell, allantoin is primarily located in the cytoplasm, and it has been detected in most biofluids. Allantoin exists in all living organisms, ranging from bacteria to humans. Allantoin is a potentially toxic compound to humans. This reaction is part of the urate degradation pathway, which is itself part of purine metabolism. Allantoinase, a zinc-dependent enzyme in the endoplasmic reticulum (that may also be found in the cell cytosol) catalyses the conversion of allantoin (5-ureidohydantoin) to allantoate by hydrolytic cleavage of the five-member hydantoin ring. The hydrolase can bind 2 manganese ions per subunit and can also use nickel and cobalt with lower activity. It catalyses the first step of the ureide allantoin degradation followed by the sequential enzymatic activity to allow complete purine breakdown without the intermediate generation of urea. In the cytosol, urea can form and is converted into ammonia in a reaction catalysed by the nickel-dependent urea hydrolase, which is involved in nitrogen recycling from ureide, purine, and arginine catabolism. The ATP-activated AMP deaminase and ectonucleotide pyrophosphatase enzymes catalyze reactions in the plant vacuole, feeding into arginine biosynthesis and the formation of ammonia, IMP, and ATP.
References
Purine Metabolism References
Ogawa T, Yoshimura K, Miyake H, Ishikawa K, Ito D, Tanabe N, Shigeoka S: Molecular characterization of organelle-type Nudix hydrolases in Arabidopsis. Plant Physiol. 2008 Nov;148(3):1412-24. doi: 10.1104/pp.108.128413. Epub 2008 Sep 24.
Pubmed: 18815383
Ferris JP, Kuder JE, Catalano AW: Photochemical reactions and the chemical evolution of purines and nicotinamide derivatives. Science. 1969 Nov 7;166(3906):765-6. doi: 10.1126/science.166.3906.765.
Pubmed: 4241847
Hung WF, Chen LJ, Boldt R, Sun CW, Li HM: Characterization of Arabidopsis glutamine phosphoribosyl pyrophosphate amidotransferase-deficient mutants. Plant Physiol. 2004 Jul;135(3):1314-23. doi: 10.1104/pp.104.040956.
Pubmed: 15266056
Watanabe S, Matsumoto M, Hakomori Y, Takagi H, Shimada H, Sakamoto A: The purine metabolite allantoin enhances abiotic stress tolerance through synergistic activation of abscisic acid metabolism. Plant Cell Environ. 2014 Apr;37(4):1022-36. doi: 10.1111/pce.12218. Epub 2013 Nov 8.
Pubmed: 24182190
Watanabe S, Nakagawa A, Izumi S, Shimada H, Sakamoto A: RNA interference-mediated suppression of xanthine dehydrogenase reveals the role of purine metabolism in drought tolerance in Arabidopsis. FEBS Lett. 2010 Mar 19;584(6):1181-6. doi: 10.1016/j.febslet.2010.02.023. Epub 2010 Feb 11.
Pubmed: 20153325
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