Plant height is an important trait that affects the crop yield and overall productivity.The Green Revolution,which began in the 1960s,brought about a remarkable surge in grain production,largely credited to the introd...Plant height is an important trait that affects the crop yield and overall productivity.The Green Revolution,which began in the 1960s,brought about a remarkable surge in grain production,largely credited to the introduction of new wheat(Triticum aestivum)and rice(Oryza sativa)varieties,specifically the dwarf variants.Short plants offer several advantages,including denser planting,resistance to lodging,and easier application of fertilizers or fungicides(Stokstad,2023).展开更多
Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels....Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.展开更多
Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the...Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mechanism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of purinergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic receptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.展开更多
The separation of a group of 17 purine and its derivatives by capillary zone electrophoresis is presented. A systematic approach was used to study the effect of pH, buffer type, organic modifiers, applied potential, s...The separation of a group of 17 purine and its derivatives by capillary zone electrophoresis is presented. A systematic approach was used to study the effect of pH, buffer type, organic modifiers, applied potential, sodium dodecyl sulfate (SDS) and cyclodextrins on the separation of these purine derivatives. An ideal condition was found for their separation, which was 30 mmol/L sodium borate buffer (pH 9–9.5), 10%(V/V) methanol buffer modifier and 20 kV. Under this condition, the 17 purine derivatives were baseline separated and the linear correlation coefficient for adenine, uric acid and 2-thioxanthine was 0. 99 over two orders of magnitude. The variation of peak areas was less than 4. 6%(n=5) and that of migration times was in the range of 0%–3%, while the samples were injected hydrodynamically at a height of 15 cm and an injection time of 8–10 s. In addition, alcohol, 1-propanol, 1-butanol and acetonitrile were also effective additives in the separation. However, SDS and various β-cyclodextrin (β-CDs) were found to do no good to their separation.展开更多
Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabo...Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabolism is an essential response to oxidative stress, and an imbalance between purine salvage and de novo biosynthesis pathways can generate damaging reactive oxygen species(ROS). Here, we examined the evolution of 117 purine metabolism-related genes to explore the accompanying molecular mechanisms of enhanced purine metabolism in mammals under high oxidative stress. We found that positively selected genes,convergent changes, and nonparallel amino acid substitutions are possibly associated with adaptation to oxidative stress in mammals. In particular, the evolution of convergent genes with c AMP and c GMP regulation roles may protect mammals from oxidative damage. Additionally, 32 genes were identified as under positive selection in cetaceans, including key purine salvage enzymes(i.e., HPRT1), suggesting improved re-utilization of non-recyclable purines avoid hypoxanthine accumulation and reduce oxidative stress. Most intriguingly, we found that six unique substitutions in cetacean xanthine dehydrogenase(XDH), an enzyme that regulates the generation of the ROS precursor xanthine oxidase(XO) during ischemic/hypoxic conditions, show enhanced enzyme activity and thermal stability and diminished XO conversion activity. These functional adaptations are likely beneficial for cetaceans by reducing radical oxygen species production during diving. In summary, our findings offer insights into the molecular and functional evolution of purine metabolism genes in mammalian oxidative stress adaptations.展开更多
Bacterial proliferation in hosts requires activation of a number of housekeeping pathways, including purine de novo biosynthesis. Although inactivation of purine biosynthesis genes can attenuate virulence, it is uncle...Bacterial proliferation in hosts requires activation of a number of housekeeping pathways, including purine de novo biosynthesis. Although inactivation of purine biosynthesis genes can attenuate virulence, it is unclear which biochemical or virulence factors are associated with the purine biosynthesis pathway in vivo. We report that inactivation of purC, a gene encoding phosphoribosylaminoimidazole-succinocarboxamide synthase, caused complete loss of virulence in Xanthomonas campestris pv. cam- pestris, the causal agent of black rot disease of cruciferous plants. The purC mutant was a purine auxotroph; it could not grow on minimal medium, whereas addition of purine derivatives, such as hypoxanthine or adenine plus guanine, restored growth of the mutant. The purC mutation also significantly enhanced the production of an unknown purine synthesis associated pigment and extracellular polysaccharides by the bacterium. In addition, comparative proteomic analyses of bacteria grown on rich and minimal media revealed that the purC mutation affected the expression levels of diverse proteins involved in purine and pyrimidine synthesis, carbon and energy metabolisms, iron uptake, proteolysis, protein secretion, and signal transduction. These results provided clues to understanding the contributions of purine synthesis to bacterial virulence and interactions with host immune systems.展开更多
This study investigated the combinatorial expression of xanthine dehydrogenase(XDH)and chaperone XdhC from Acinetobacter baumannii and Rhodobacter capsulatus and their applications in decreasing purine content in the ...This study investigated the combinatorial expression of xanthine dehydrogenase(XDH)and chaperone XdhC from Acinetobacter baumannii and Rhodobacter capsulatus and their applications in decreasing purine content in the beer,beef and yeast.Naturally occurring xdhABC gene clusters of A.baumannii CICC 10254 and R.capsulatus CGMCC 1.3366 as well as two refactored clusters constructed by exchanging their xdhC genes were overexpressed in Escherichia coli and purified to near homogeneity.RcXDH chaperoned by AbXdhC showed nearly the same catalytic performance as that by RcXdhC,except for the decreased substrate affinity.While the AbXDH co-expressed with RcXdhC displayed enhanced acidic adaptation but weakened catalytic activity.All the XDHs degraded purines in beer,beef and yeast extract effectively,indicating potential applications in low-purine foods to prevent hyperuricemia and gout.The study also presents a method for exploiting the better chaperone XdhC and novel XDHs by functional complement activity using existing XdhCs such as RcXdhC.展开更多
The purines constitute a family of inter-related compounds that serve a broad range of important intracellular and extracellular biological functions.In particular,adenosine triphosphate(ATP)and its metabolite and pre...The purines constitute a family of inter-related compounds that serve a broad range of important intracellular and extracellular biological functions.In particular,adenosine triphosphate(ATP)and its metabolite and precursor,adenosine,regulate a wide variety of cellular and systems-level physiological processes extending from ATP acting as the cellular energy currency,to the adenosine arising from the depletion of cellular ATP and responding to reduce energy demand and hence to preserve ATP during times of metabolic stress.This inter-relationship provides opportunities for both the diagnosis of energy depletion during conditions such as stroke,and the replenishment of ATP after such events.In this review we address these opportunities and the broad potential of purines as diagnostics and restorative agents.展开更多
C8-Alkyl-substituted purine analogues were synthesized through direct alkylation of 8-H purine with tetrahydrofuran in the presence of Co catalyst in one step. The reactions gave a series of novel C8-oxygen heterocycl...C8-Alkyl-substituted purine analogues were synthesized through direct alkylation of 8-H purine with tetrahydrofuran in the presence of Co catalyst in one step. The reactions gave a series of novel C8-oxygen heterocyclic alkyl purine compounds in good yields under mild reaction conditions by the readily available alkylating reagents, providing a complementary route to the classical coupling reactions for the synthesis of C8-alkyl-substituted purine analogues.展开更多
We measured the erythrocyte levels of principal nucleotides (ATP, ADP, AMP, GTP, GDP, GMP, IMP), nucleosides (Ado, Guo, Ino) and Hyp with HPLC. Purine concentrations were determined in the erythrocytes of 36 type 1 an...We measured the erythrocyte levels of principal nucleotides (ATP, ADP, AMP, GTP, GDP, GMP, IMP), nucleosides (Ado, Guo, Ino) and Hyp with HPLC. Purine concentrations were determined in the erythrocytes of 36 type 1 and 40 type 2 diabetic patients. The increased dephosphorylation of adenine and guanine nucleotides, indicated by increased Ado, Ino, Guo and Hyp concentrations as the products of purine nucleotide degradation, suggests serious energy metabolism disruptions in diabetes. An increase in AMP, GMP, IMP concentrations, as well as a decrease in AEC and GEC values, points to significant alterations in erythrocyte purine nucleotide concentration.展开更多
An efficient and regioselective synthesis of N-9 alkoxyalkylated purine nucleoside derivatives was achieved via the N-alkoxyalkylation of purine rings with vinyl ethers catalyzed by L-ProT.The advantages of this proto...An efficient and regioselective synthesis of N-9 alkoxyalkylated purine nucleoside derivatives was achieved via the N-alkoxyalkylation of purine rings with vinyl ethers catalyzed by L-ProT.The advantages of this protocol include good to excellent yield,mild reaction condition,and simple manipulation.A plausible mechanism for the transformation was given.展开更多
In this study, the chemical analysis of the marine sponge spieces, Haliclona cymaeformis, collected from the South China Sea was carried out, Two pairs of regioisomers of alkyl substitutional 6-oxy purine alkaloids(1a...In this study, the chemical analysis of the marine sponge spieces, Haliclona cymaeformis, collected from the South China Sea was carried out, Two pairs of regioisomers of alkyl substitutional 6-oxy purine alkaloids(1a/1b and 2a/2b) were isolated. All of them possess two structural moieties, a 6-oxy purine nucleus and a pentan-2-one or hexan-2-one alkyl chain. Among them, 1a and 2a are the major N-9-substitutional regioisomers, and 1b and 2b are the minor N-7-substitutional regioisomers.展开更多
Xanthine dehydrogenase(XDH) is a crucial enzyme involved in purine metabolism. To evaluate the effect of XDH deficiency on rice growth during dark treatment, wild type(WT) Nipponbare(Oryza sativa L.) and two independe...Xanthine dehydrogenase(XDH) is a crucial enzyme involved in purine metabolism. To evaluate the effect of XDH deficiency on rice growth during dark treatment, wild type(WT) Nipponbare(Oryza sativa L.) and two independent transgenic lines with severe RNAi suppression(xdh3 and xdh4) were used in the present experiment. Under normal growth conditions, chlorophyll levels and biomass were indistinguishable between WT and the two RNAi transgenic lines, but XDH enzyme activity and ureide levels were suppressed in XDH RNAi transgenic lines. When XDH RNAi transgenic lines were subjected to dark treatment, chlorophyll content and biomass were significantly decreased, while O~–· production rate and malonaldehyde(MDA) were significantly increased compared to WT. The spraying test of exogenous allantoin raised chlorophyll content and biomass and reduced O~–· production rate and MDA in WT and both transgenic lines, and it also simultaneously reduced differences between RNAi and WT plants caused by XDH deficiency in growth potential and anti-oxidative capacity under dark treatment. These results suggested that fully functional purine metabolism plays an important role in reducing the sensitivity of rice seedlings to dark stress.展开更多
Recently, hydrogen-bonding has attracted extensive attention in the design of chromophores. Here, a new class of hydrogen-bond locked purine chromophores(HOPs) were reported by introducing a hydroxyphenyl group into t...Recently, hydrogen-bonding has attracted extensive attention in the design of chromophores. Here, a new class of hydrogen-bond locked purine chromophores(HOPs) were reported by introducing a hydroxyphenyl group into the C(6) position of purine. The intramolecular hydrogen bond plays a dominant role to light up these probes. As a bonus, HOPs show high photostability. Moreover, HOPs exhibit remarkable capability for the specific lipid droplets imaging in living cells with excellent biocompatibility and are also potential for diagnosing fatty liver diseases. These results bring important new insights into the photophysics of the purine-based chromophores and provide a new scaffold with high photostability for bioimaging.展开更多
An efficient procedure for N-alkylation of pyrimidines and purines in the presence of tetra-n-butylammonium hydroxide（TBAH） is described. The method is very practical and the alkylation can occur at room temperature...An efficient procedure for N-alkylation of pyrimidines and purines in the presence of tetra-n-butylammonium hydroxide（TBAH） is described. The method is very practical and the alkylation can occur at room temperature and the yields of the N-alkyl pyrimidines and purines were found to be excellent.展开更多
Two bridged purine dinucleosides, bis(2-N-acetyl-6-N-alkylylene-2,6-diaminopurine-2',3',5'-triacetyl-beta-D-ribofuranoside), were synthesized fi om the reaction of the key medium 3, 2-acetylamino-6-[1-(1,2...Two bridged purine dinucleosides, bis(2-N-acetyl-6-N-alkylylene-2,6-diaminopurine-2',3',5'-triacetyl-beta-D-ribofuranoside), were synthesized fi om the reaction of the key medium 3, 2-acetylamino-6-[1-(1,2,4-triazolyl)]-purine-2',3',5'-triacetyl-beta-D-ribofuranoside with dialkylamine.展开更多
Most riboswitches are characterized by two components, an aptamer domain that folds into a unique ligand binding pocket to interact with the ligand, and an expression platform that converts folding changes in the apta...Most riboswitches are characterized by two components, an aptamer domain that folds into a unique ligand binding pocket to interact with the ligand, and an expression platform that converts folding changes in the aptamer into changes in gene expression. Using the recently developed systematic helix-based computational method, we theoretically studied the refolding and co-transcriptional folding behaviors of the purine riboswitch aptamers from Bacillus subtilis xpt-pbu X guanine riboswitch and Vibrio vulnificus add adenine riboswitch. Despite several intermediate structures persisting a short time during the transcription, helices P2, P3 and P1 fold in turn for both aptamers. Although some misfolded structures are observed during the refolding process, the RNAs can fold into the ligand binding pocket structure containing helices P2, P3 and P1 within a few seconds, suggesting the aptamer domains are highly evolved. The purine riboswitch aptamers can quickly fold into the ligand binding pocket structure even at a high transcription speed, possibly because formation of this structure is the necessary prerequisite for the riboswitch to bind its ligand and then regulate relevant gene expression.展开更多
The photocatalyzed synthesis of 9-arylpurines has been developed using 9H-purines and non-activated arenes.This method is highly atom economical using an acridinium photocatalyst induced by visible light under air atm...The photocatalyzed synthesis of 9-arylpurines has been developed using 9H-purines and non-activated arenes.This method is highly atom economical using an acridinium photocatalyst induced by visible light under air atmosphere at room temperature.It employs no metal or external oxidant for the synthesis of9-arylpurine derivatives.展开更多
The aim of this study was to determine the time course of changes in extracellular fluid (ECF) concentrations of purines, amino acids, monoamines, and their metabolites in the striatum of rats during ischemia and repe...The aim of this study was to determine the time course of changes in extracellular fluid (ECF) concentrations of purines, amino acids, monoamines, and their metabolites in the striatum of rats during ischemia and reperfusion, using intracerebral microdialysis as the sampling technique. In rats subjected to 20 min forebrain ischemia by four-vessel occlusion, the concentrations of adenosine (Ade), inosine (Ino) and hypoxanthine (Hyp) were found to rise markedly. These changes were accompanied by dramatically elevated levels of aspartate (Asp), glutamate (Glu), taurine (Tau), γ-aminobutyric acid (GABA), dopamine (DA) and norepinephrine (NE), all of which gradually returned to baseline following reperfusion. Concomitantly, the levels of metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) . homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA) and xanthine (Xan) decreased during ischemia and gradually recovered 60～ 90 min after reperfusion. It was concluded that during global brain ischemia, the ECF is flooded with both potentially harmful (e. g. Asp, Glu, DA) and protective (e. g. Tau, GABA, Ade) agents.展开更多
6-mercaptopurine(6-MP),a purine derivative(3,7-dihydropurine-6-thione),has been utilized as an effective immunosuppressive drug for clinically treating leukemia and other autoimmune diseases[1].6-MP and its correspond...6-mercaptopurine(6-MP),a purine derivative(3,7-dihydropurine-6-thione),has been utilized as an effective immunosuppressive drug for clinically treating leukemia and other autoimmune diseases[1].6-MP and its corresponding metabolites can suppress the function of RnaseH,and thus they are cytotoxic and threaten the human health[2].Therefore,the accurate quantification of 6-MP is crucial.To date,researchers continue to expend considerable effort in developing 6-MP detection methods.Fluorescence analysis eliminates disadvantages,such as toxic solvents,expensive equipment.展开更多
基金supported by grants from the National Natural Science Foundation of China(32270290)the Shanghai Engineering Research Center of Plant Germplasm Resources(17DZ2252700).
文摘Plant height is an important trait that affects the crop yield and overall productivity.The Green Revolution,which began in the 1960s,brought about a remarkable surge in grain production,largely credited to the introduction of new wheat(Triticum aestivum)and rice(Oryza sativa)varieties,specifically the dwarf variants.Short plants offer several advantages,including denser planting,resistance to lodging,and easier application of fertilizers or fungicides(Stokstad,2023).
文摘Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.
基金This work was financially supported by the National Natural Science Foundation of China(Grant Nos.:82074323 and 81673572)Key Research and Development Program of Shanxi Province(Grant No.:202102130501010)+2 种基金Innovation Project for Graduate Students in Shanxi Province(Grant No.:2022Y162)the Major Science and Technology Project for“Significant New Drugs Creation”(Grant No.:2017ZX09301047)Research Project Supported by Shanxi Scholarship Council of China(Grant No.:2020019).
文摘Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mechanism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of purinergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic receptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.
基金The National Natural Science Foundation of China(20173040)
文摘The separation of a group of 17 purine and its derivatives by capillary zone electrophoresis is presented. A systematic approach was used to study the effect of pH, buffer type, organic modifiers, applied potential, sodium dodecyl sulfate (SDS) and cyclodextrins on the separation of these purine derivatives. An ideal condition was found for their separation, which was 30 mmol/L sodium borate buffer (pH 9–9.5), 10%(V/V) methanol buffer modifier and 20 kV. Under this condition, the 17 purine derivatives were baseline separated and the linear correlation coefficient for adenine, uric acid and 2-thioxanthine was 0. 99 over two orders of magnitude. The variation of peak areas was less than 4. 6%(n=5) and that of migration times was in the range of 0%–3%, while the samples were injected hydrodynamically at a height of 15 cm and an injection time of 8–10 s. In addition, alcohol, 1-propanol, 1-butanol and acetonitrile were also effective additives in the separation. However, SDS and various β-cyclodextrin (β-CDs) were found to do no good to their separation.
基金supported by the National Natural Science Foundation of China(NSFC)(31900310 to R.T.)Key Project of the NSFC(32030011 and 31630071 to G.Y.)+2 种基金NSFC(31950410545 to I.S.)Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Jiangsu Specially-Appointed Professors Program(to I.S.)。
文摘Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabolism is an essential response to oxidative stress, and an imbalance between purine salvage and de novo biosynthesis pathways can generate damaging reactive oxygen species(ROS). Here, we examined the evolution of 117 purine metabolism-related genes to explore the accompanying molecular mechanisms of enhanced purine metabolism in mammals under high oxidative stress. We found that positively selected genes,convergent changes, and nonparallel amino acid substitutions are possibly associated with adaptation to oxidative stress in mammals. In particular, the evolution of convergent genes with c AMP and c GMP regulation roles may protect mammals from oxidative damage. Additionally, 32 genes were identified as under positive selection in cetaceans, including key purine salvage enzymes(i.e., HPRT1), suggesting improved re-utilization of non-recyclable purines avoid hypoxanthine accumulation and reduce oxidative stress. Most intriguingly, we found that six unique substitutions in cetacean xanthine dehydrogenase(XDH), an enzyme that regulates the generation of the ROS precursor xanthine oxidase(XO) during ischemic/hypoxic conditions, show enhanced enzyme activity and thermal stability and diminished XO conversion activity. These functional adaptations are likely beneficial for cetaceans by reducing radical oxygen species production during diving. In summary, our findings offer insights into the molecular and functional evolution of purine metabolism genes in mammalian oxidative stress adaptations.
基金supported by the grants from the National Basic Research Program of the Ministry of Science and Technology of China(No.2011CB100700)the National Science Foundation of China(Nos.31100065 and 31070081)the Basic Research of Frontiers of the Chinese Academy of Sciences(No.KSCX2-EW-J-6)
文摘Bacterial proliferation in hosts requires activation of a number of housekeeping pathways, including purine de novo biosynthesis. Although inactivation of purine biosynthesis genes can attenuate virulence, it is unclear which biochemical or virulence factors are associated with the purine biosynthesis pathway in vivo. We report that inactivation of purC, a gene encoding phosphoribosylaminoimidazole-succinocarboxamide synthase, caused complete loss of virulence in Xanthomonas campestris pv. cam- pestris, the causal agent of black rot disease of cruciferous plants. The purC mutant was a purine auxotroph; it could not grow on minimal medium, whereas addition of purine derivatives, such as hypoxanthine or adenine plus guanine, restored growth of the mutant. The purC mutation also significantly enhanced the production of an unknown purine synthesis associated pigment and extracellular polysaccharides by the bacterium. In addition, comparative proteomic analyses of bacteria grown on rich and minimal media revealed that the purC mutation affected the expression levels of diverse proteins involved in purine and pyrimidine synthesis, carbon and energy metabolisms, iron uptake, proteolysis, protein secretion, and signal transduction. These results provided clues to understanding the contributions of purine synthesis to bacterial virulence and interactions with host immune systems.
基金funded by the National Natural Science Foundation of China(21868003)the Guangxi Natural Science Foundation(2018AD19022,2017GXNSFAA198265)the Nanning Science and Technology Development Project(2017014).
文摘This study investigated the combinatorial expression of xanthine dehydrogenase(XDH)and chaperone XdhC from Acinetobacter baumannii and Rhodobacter capsulatus and their applications in decreasing purine content in the beer,beef and yeast.Naturally occurring xdhABC gene clusters of A.baumannii CICC 10254 and R.capsulatus CGMCC 1.3366 as well as two refactored clusters constructed by exchanging their xdhC genes were overexpressed in Escherichia coli and purified to near homogeneity.RcXDH chaperoned by AbXdhC showed nearly the same catalytic performance as that by RcXdhC,except for the decreased substrate affinity.While the AbXDH co-expressed with RcXdhC displayed enhanced acidic adaptation but weakened catalytic activity.All the XDHs degraded purines in beer,beef and yeast extract effectively,indicating potential applications in low-purine foods to prevent hyperuricemia and gout.The study also presents a method for exploiting the better chaperone XdhC and novel XDHs by functional complement activity using existing XdhCs such as RcXdhC.
文摘The purines constitute a family of inter-related compounds that serve a broad range of important intracellular and extracellular biological functions.In particular,adenosine triphosphate(ATP)and its metabolite and precursor,adenosine,regulate a wide variety of cellular and systems-level physiological processes extending from ATP acting as the cellular energy currency,to the adenosine arising from the depletion of cellular ATP and responding to reduce energy demand and hence to preserve ATP during times of metabolic stress.This inter-relationship provides opportunities for both the diagnosis of energy depletion during conditions such as stroke,and the replenishment of ATP after such events.In this review we address these opportunities and the broad potential of purines as diagnostics and restorative agents.
基金the National Natural Science Foundation of China (No. 21202039)the Program for Science & Technology Innovation Talents in Universities of Henan Province (No. 13HASTIT013)the Foundation for University Young Key Teacher by Henan Province of China (No. 2011GGJS132)
文摘C8-Alkyl-substituted purine analogues were synthesized through direct alkylation of 8-H purine with tetrahydrofuran in the presence of Co catalyst in one step. The reactions gave a series of novel C8-oxygen heterocyclic alkyl purine compounds in good yields under mild reaction conditions by the readily available alkylating reagents, providing a complementary route to the classical coupling reactions for the synthesis of C8-alkyl-substituted purine analogues.
文摘We measured the erythrocyte levels of principal nucleotides (ATP, ADP, AMP, GTP, GDP, GMP, IMP), nucleosides (Ado, Guo, Ino) and Hyp with HPLC. Purine concentrations were determined in the erythrocytes of 36 type 1 and 40 type 2 diabetic patients. The increased dephosphorylation of adenine and guanine nucleotides, indicated by increased Ado, Ino, Guo and Hyp concentrations as the products of purine nucleotide degradation, suggests serious energy metabolism disruptions in diabetes. An increase in AMP, GMP, IMP concentrations, as well as a decrease in AEC and GEC values, points to significant alterations in erythrocyte purine nucleotide concentration.
基金the Natural Science Foundation of Zhejiang Province(No.LY13B020015)Zhejiang Key Innovation Team of Green Pharmaceutical Technology(No.2012R10043-07) for financial support
文摘An efficient and regioselective synthesis of N-9 alkoxyalkylated purine nucleoside derivatives was achieved via the N-alkoxyalkylation of purine rings with vinyl ethers catalyzed by L-ProT.The advantages of this protocol include good to excellent yield,mild reaction condition,and simple manipulation.A plausible mechanism for the transformation was given.
基金supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No.16KJB350005)the Yangzhou University Foundation for Fostering Talents in the Science and Technology Innovation (No.2016CXJ052)+1 种基金the National Natural Science Foundation of China (Nos.81703411,U1606403)the Taishan Scholars Program,China
文摘In this study, the chemical analysis of the marine sponge spieces, Haliclona cymaeformis, collected from the South China Sea was carried out, Two pairs of regioisomers of alkyl substitutional 6-oxy purine alkaloids(1a/1b and 2a/2b) were isolated. All of them possess two structural moieties, a 6-oxy purine nucleus and a pentan-2-one or hexan-2-one alkyl chain. Among them, 1a and 2a are the major N-9-substitutional regioisomers, and 1b and 2b are the minor N-7-substitutional regioisomers.
基金supported by the National Natural Science Foundation of China (31560350 and 31760350)the Science and Technology Program of Jiangxi, China (20171ACF60018)
文摘Xanthine dehydrogenase(XDH) is a crucial enzyme involved in purine metabolism. To evaluate the effect of XDH deficiency on rice growth during dark treatment, wild type(WT) Nipponbare(Oryza sativa L.) and two independent transgenic lines with severe RNAi suppression(xdh3 and xdh4) were used in the present experiment. Under normal growth conditions, chlorophyll levels and biomass were indistinguishable between WT and the two RNAi transgenic lines, but XDH enzyme activity and ureide levels were suppressed in XDH RNAi transgenic lines. When XDH RNAi transgenic lines were subjected to dark treatment, chlorophyll content and biomass were significantly decreased, while O~–· production rate and malonaldehyde(MDA) were significantly increased compared to WT. The spraying test of exogenous allantoin raised chlorophyll content and biomass and reduced O~–· production rate and MDA in WT and both transgenic lines, and it also simultaneously reduced differences between RNAi and WT plants caused by XDH deficiency in growth potential and anti-oxidative capacity under dark treatment. These results suggested that fully functional purine metabolism plays an important role in reducing the sensitivity of rice seedlings to dark stress.
基金financially supported by the National Natural Science Foundation of China (Nos. 22077088, 21877082,U21A20308)the Foundation from the Science and Technology Department of Sichuan Province (Nos. 2020JDJQ0017,2021YFH0132, 2020ZHCG0097)。
文摘Recently, hydrogen-bonding has attracted extensive attention in the design of chromophores. Here, a new class of hydrogen-bond locked purine chromophores(HOPs) were reported by introducing a hydroxyphenyl group into the C(6) position of purine. The intramolecular hydrogen bond plays a dominant role to light up these probes. As a bonus, HOPs show high photostability. Moreover, HOPs exhibit remarkable capability for the specific lipid droplets imaging in living cells with excellent biocompatibility and are also potential for diagnosing fatty liver diseases. These results bring important new insights into the photophysics of the purine-based chromophores and provide a new scaffold with high photostability for bioimaging.
基金Supported by the National Natural Science Foundation of China(No. 20172007) and the"985"Programs, Ministry of Educa-tion of China
文摘An efficient procedure for N-alkylation of pyrimidines and purines in the presence of tetra-n-butylammonium hydroxide（TBAH） is described. The method is very practical and the alkylation can occur at room temperature and the yields of the N-alkyl pyrimidines and purines were found to be excellent.
文摘Two bridged purine dinucleosides, bis(2-N-acetyl-6-N-alkylylene-2,6-diaminopurine-2',3',5'-triacetyl-beta-D-ribofuranoside), were synthesized fi om the reaction of the key medium 3, 2-acetylamino-6-[1-(1,2,4-triazolyl)]-purine-2',3',5'-triacetyl-beta-D-ribofuranoside with dialkylamine.
基金Supported by the National Natural Science Foundation of China(31600592)Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization,Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains(2017BX08)
文摘Most riboswitches are characterized by two components, an aptamer domain that folds into a unique ligand binding pocket to interact with the ligand, and an expression platform that converts folding changes in the aptamer into changes in gene expression. Using the recently developed systematic helix-based computational method, we theoretically studied the refolding and co-transcriptional folding behaviors of the purine riboswitch aptamers from Bacillus subtilis xpt-pbu X guanine riboswitch and Vibrio vulnificus add adenine riboswitch. Despite several intermediate structures persisting a short time during the transcription, helices P2, P3 and P1 fold in turn for both aptamers. Although some misfolded structures are observed during the refolding process, the RNAs can fold into the ligand binding pocket structure containing helices P2, P3 and P1 within a few seconds, suggesting the aptamer domains are highly evolved. The purine riboswitch aptamers can quickly fold into the ligand binding pocket structure even at a high transcription speed, possibly because formation of this structure is the necessary prerequisite for the riboswitch to bind its ligand and then regulate relevant gene expression.
基金supported by Basic and Applied Basic Research Foundation of Guangdong Province in China(No.2021A1515012349)。
文摘The photocatalyzed synthesis of 9-arylpurines has been developed using 9H-purines and non-activated arenes.This method is highly atom economical using an acridinium photocatalyst induced by visible light under air atmosphere at room temperature.It employs no metal or external oxidant for the synthesis of9-arylpurine derivatives.
文摘The aim of this study was to determine the time course of changes in extracellular fluid (ECF) concentrations of purines, amino acids, monoamines, and their metabolites in the striatum of rats during ischemia and reperfusion, using intracerebral microdialysis as the sampling technique. In rats subjected to 20 min forebrain ischemia by four-vessel occlusion, the concentrations of adenosine (Ade), inosine (Ino) and hypoxanthine (Hyp) were found to rise markedly. These changes were accompanied by dramatically elevated levels of aspartate (Asp), glutamate (Glu), taurine (Tau), γ-aminobutyric acid (GABA), dopamine (DA) and norepinephrine (NE), all of which gradually returned to baseline following reperfusion. Concomitantly, the levels of metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) . homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA) and xanthine (Xan) decreased during ischemia and gradually recovered 60～ 90 min after reperfusion. It was concluded that during global brain ischemia, the ECF is flooded with both potentially harmful (e. g. Asp, Glu, DA) and protective (e. g. Tau, GABA, Ade) agents.
基金support of Taiyuan Institute of Technology Scientific Research Initial Funding,China(Grant No.:2022KJ058)the Basic Research Project of Shanxi Province,China(Project No.:202203021212331)+1 种基金the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi,China(Program Nos.:2022L529 and 2022L532)the Fund for Shanxi“1331”Project,China.
文摘6-mercaptopurine(6-MP),a purine derivative(3,7-dihydropurine-6-thione),has been utilized as an effective immunosuppressive drug for clinically treating leukemia and other autoimmune diseases[1].6-MP and its corresponding metabolites can suppress the function of RnaseH,and thus they are cytotoxic and threaten the human health[2].Therefore,the accurate quantification of 6-MP is crucial.To date,researchers continue to expend considerable effort in developing 6-MP detection methods.Fluorescence analysis eliminates disadvantages,such as toxic solvents,expensive equipment.
