Guanine Deaminase Functions as Dihydropterin Deaminase in the Biosynthesis of Aurodrosopterin, a Minor Red Eye Pigment of Drosophila

Cheng

American Journal of Physiology-Cell Physiology

et al. 2013

The aim of this investigation was to test the hypothesis that extracellular guanosine regulates extracellular adenosine levels. Rat preglomerular vascular smooth muscle cells were incubated with adenosine, guanosine, or both. Guanosine (30 μmol/l) per se had little effect on extracellular adenosine levels. Extracellular adenosine levels 1 h after addition of adenosine (3 μmol/l) were 0.125 ± 0.020 μmol/l, indicating rapid disposition of extracellular adenosine. Extracellular adenosine levels 1 h after addition of adenosine (3 μmol/l) plus guanosine (30 μmol/l) were 1.173 ± 0.061 μmol/l, indicating slow disposition of extracellular adenosine. Cell injury increased extracellular levels of endogenous adenosine and guanosine, and the effects of cell injury on endogenous extracellular adenosine were modulated by altering the levels of endogenous extracellular guanosine with exogenous purine nucleoside phosphorylase (converts guanosine to guanine) or 8-aminoguanosine (inhibits purine nucleoside phosphorylase). Extracellular guanosine also slowed the disposition of extracellular adenosine in rat preglomerular vascular endothelial cells, mesangial cells, cardiac fibroblasts, and kidney epithelial cells and in human aortic and coronary artery vascular smooth muscle cells and coronary artery endothelial cells. The effects of guanosine on adenosine levels were not mimicked or attenuated by 5-iodotubericidin (adenosine kinase inhibitor), erythro-9-(2-hydroxy-3-nonyl)-adenine (adenosine deaminase inhibitor), 5-aminoimidazole-4-carboxamide (guanine deaminase inhibitor), aristeromycin (S-adenosylhomocysteine hydrolase inhibitor), low sodium (inhibits concentrative nucleoside transporters), S-(4-nitrobenzyl)-6-thioinosine [inhibits equilibrative nucleoside transporter (ENT) type 1], zidovudine (inhibits ENT type 2), or acadesine (known modulator of adenosine levels). Guanosine also increases extracellular inosine, uridine, thymidine, and cytidine, yet decreases extracellular uric acid. In conclusion, extracellular guanosine regulates extracellular adenosine levels.

Section: Discussionmentioning

confidence: 97%

“…Next, we entertained the possibility that adenosine and guanosine could interact at the level of guanine deaminase (48). Therefore we examined in rat preglomerular vascular smooth muscle cells the role of this enzyme in mediating the effects of guanosine on adenosine levels.…”

Section: Extracellular Guanosine Inhibits Adenosine Disposition In Ramentioning

confidence: 99%

Extracellular guanosine regulates extracellular adenosine levels

Cheng

American Journal of Physiology-Cell Physiology

et al. 2013

“…The biosynthesis of drosopterins is accomplished by a series of enzymatic and nonenzymatic reactions (Fig. 1) (7). The first step in the biosynthesis of drosopterins is the conversion of GTP into 7,8‐dihydroneopterin triphosphate (H 2 ‐NTP) with the release of formic acid by GTP cyclohydrolase I (GTPCH I; EC 3.5.4.16) (8).…”

Section: Biosynthetic Pathway Of Drosopterinsmentioning

confidence: 99%

“…Aurodrosopterin and isoaurodrosopterin are also produced in a similar fashion by the nonenzymatic one‐to‐one condensation of 7,8‐dihydrolumazine with PDA under acidic conditions (4). 7,8‐Dihydrolumazine is produced from 7,8‐dihydropterin by deamination that is catalyzed by dihydropterin deaminase (EC 3.5.4.11) (7, 14).…”

Section: Biosynthetic Pathway Of Drosopterinsmentioning

confidence: 99%

Biosynthesis of drosopterins, the red eye pigments of Drosophila melanogaster

Kim

Yim

2013

IUBMB Life

Self Cite

Drosophila melanogaster has red eyes. Scientists have been curious about the biosynthesis of the red eye pigments and have completed a number of investigations on these compounds. Scientific contributions made over the past 50 years have improved our understanding of the red eye pigments. Researchers have elucidated the chemical structures of some pigments and have successfully purified and identified the enzymes that participate in the biosynthesis of the red eye pigments. In this article, we will review the characteristics of the Drosophila red eye pigments and of the enzymes and genes involved in its biosynthetic pathway. V C 2013 IUBMB Life, 65(4): [334][335][336][337][338][339][340] 2013

“…However, the inhibitory effect of guanosine was less than that observed by Kim et al [2009]. Food contains different amounts of RNA, DNA, nucleotides and nucleosides [Wolfram and Colling, 1987] and the reduction of the negative effect of guanosine on the recombinant enzyme should be advantageous in its application for food treatment.…”

Section: ) Was Homologous To the Conserved Sequence Pgx[v/i] Dxh[t/mentioning

confidence: 99%

<b><i>Arxula adeninivorans</i></b> Recombinant Guanine Deaminase and Its Application in the Production of Food with Low Purine Content

Trautwein-Schult

Jankowska²,

Cordes³

et al. 2014

Microb Physiol

Purines of exogenous and endogenous sources are degraded to uric acid in human beings. Concentrations >6.8 mg uric acid/dl serum cause hyperuricemia and its symptoms. Pharmaceuticals and the reduction of the intake of purine-rich food are used to control uric acid levels. A novel approach to the latter proposition is the enzymatic reduction of the purine content of food by purine-degrading enzymes. Here we describe the production of recombinant guanine deaminase by the yeast Arxula adeninivorans LS3 and its application in food. In media supplemented with nitrogen sources hypoxanthine or adenine, guanine deaminase (AGDA) gene expression is induced and intracellular accumulation of guanine deaminase (Agdap) protein occurs. The characteristics of the guanine deaminase isolated from wild-type strain LS3 and a transgenic strain expressing the AGDA gene under control of the strong constitutive TEF1 promoter were determined and compared. Both enzymes were dimeric and had temperature optima of 55°C with high substrate specificity for guanine and localisation in both the cytoplasm and vacuole of yeast. The enzyme was demonstrated to reduce levels of guanine in food. A mixture of guanine deaminase and other purine degradation enzymes will allow the reduction of purines in purine-rich foods.