Urea Metabolism Research Articles

Degradation of Diclofenac in Urine by Electro-Permanganate Process Driven by Microbial Fuel Cells

A novel microbial fuel cell-assisted electro-permanganate process (MFC-PM) was proposed for enhanced diclofenac degradation compared to that of the permanganate oxidation process. By utilizing eco-friendly bio-electricity in situ, the MFC-PM process could activate the simultaneous anodic biological metabolism of urea and the cathodic electro-permanganate process. Density functional analysis and experimental evidence revealed the reactive manganese species (Mn(VII)aq, Mn(VI)aq, Mn(V)aq, and Mn(III)aq), generated via single electron transfer, contributed to diclofenac degradation in the cathodic chamber. The sites of diclofenac with a high Fukui index were preferable to be attacked by reactive manganese species, and diclofenac degradation was mainly accomplished through the ring hydroxylation, ring opening, and decarboxylation processes. Biological detection revealed clostridia were the primary electron donor in the anode chamber in an anaerobic environment. Furthermore, maximum output power density of 1.49 W m−3 and the optimal removal of 94.75% diclofenac were obtained within 20 min under the conditions of pH = 3.0, [DCF]0 = 60 µM, and [PM]0 = 30 µM. Diclofenac removal efficiency increased with external resistance, higher PM dosage, and lower catholyte pH. In addition, the MFC-PM process displayed excellent applicability in urine and other background substances. The MFC-PM process provided an efficient and energy-free bio-electricity catalytic permanganate oxidation technology for enhancing diclofenac degradation.

Molecular Insights into Beneficial Effects of Tea-Plant Growth and Selenium Enrichment by Herbaspirillum camelliae

Herbaspirillum camelliae WT00C, as a tea-plant endophytic bacterium, not only colonizes specifically in tea plants but also promotes tea-plant growth and selenium enrichment. Different from diazotrophic endophytes H. seropedicae, H. frisingense and H. rubrisubalbicans, H. camelliae WT00C does not display nitrogen-fixing activity. To understand the molecular mechanisms of promoting the growth of tea plant and Se-enrichment, we sequenced and annotated the genome of H. camelliae WT00C. The results showed that the genome was composed of 6,079,821 base pairs with a total of 5,537 genes. The genomic survey also revealed that H. camelliae WT00C was a multifunctional bacterium metabolizing a variety of carbon and nitrogen sources and defending against biotic and abiotic stress. Although this bacterium did not have intact nitrogen-fixing genes, its genome held the genes responsible for indole-3-acetic acid (IAA) biosynthesis, 1-aminocyclopropane-1-carboxylate (ACC) deamination, siderophore synthesis, ammonia formation, urea metabolism, glutathione and selenocompound metabolisms. Biosynthesis of IAA, siderophore, ammonia, urea and ACC deaminase could explain why two bacterial strains promote tea-plant growth and development. Selenocompound metabolism in this bacterium might also benefit tea-plant growth and Se-enrichment. In addition, the genome of H. camelliae also contained a multitude of protein secretion systems T1SS, T3SS, T4SS and T6SS, in which T4SS did not exhibit in other members of the genus Herbaspirillum.

Alteration in Metabolic Cost of Blood Urea, Serum Albumin and Oxidative Stress Induced by Oral Contraceptive Pills (OCP) among Elite Females

Background: For controlling unwilling pregnancy, sustaining gorgeousness and good health, among the elite level female athletes the use of contraceptive pills is quite common. Objective: Oxidative stress in female athletes is understudied. This research study was carried out in order to assess the alteration in metabolic rate of blood urea, bilirubin and oxidative stress induced by Levonorgestrel and Ethinylestradiol (oral contraceptive pills). The outcome of the study will reveal the impact of oral contraceptive pills on the overall health of the females. 
 Methods: User and non-user of oral contraceptive pills were included as participants of the study. Sixty elite level female athletes using Levonorgestrel and Ethinylestradiol were recruited as experimental group and twenty four female (non-users) as a control group were taken as sample of the study. Blood sample (5ml) was taken from all the subjects. Blood urea and bilirubin metabolism were estimated through kidney functional test and for the measurement of oxidative stress FRAP assay was used. The data obtained through kidney functional tests and FRAP assay were processed through statistical package for social sciences (SPSS, Version 23.0)
 Results: A significant difference was found between control and experimental subjects in FRAP values because (t (82) = 3.236, P <0.05). The mean value of subject was 110.54 and control was 137.95 in FRAP the mean value of subject is less than the mean value of control (509.3 <700.7). In case of bilirubin and serum albumin no difference was noted between control and experimental group as the value of significance is greater than 0.05.
 Conclusion: Based on the analysis, the researcher concluded that oral contraceptive pills produced significant rise in oxidative stress, thus affecting the overall health of elite female athletes.

Urea as a By-Product of Ammonia Metabolism Can Be a Potential Serum Biomarker of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is highly malignant; nearly half of the new cases and deaths are in China. The poor prognosis of HCC is mainly due to late diagnosis; many new biomarkers have been developed for HCC diagnosis. However, few markers are quickly translated into clinical practice; early and differential diagnosis of HCC from cirrhosis and/or hepatitis is still a clinical challenge. Metabolomics and biochemical methods were used to reveal specific serum biomarkers of HCC. Most of the elevated metabolites in HCC and HBV patients were overlapped compared with controls. Urea was the specifically elevated serum biomarker of HCC patients. Moreover, urea combined with AFP and CEA can improve the sensitivity of HCC diagnosis. The plasma ammonia of HCC patients was significantly higher than healthy controls. Co-culture cell model revealed normal liver cells cooperated with cancer cells to metabolize ammonia into urea. The urea metabolism in cancer cells marginally depended on the expression of CPS1. However, the expression of CPS1 did not change with ammonium chloride, which might regulate the urea cycle through enzyme activity. The urea cycle could detoxify high concentrations of ammonia to promote cancer cell proliferation. Therefore, urea was a by-product of ammonia metabolism and could be a potential serum biomarker for HCC. The combined application of metabolomics and biochemical methods can discover new biomarkers for the early diagnosis of HCC and be quickly applied to clinical diagnosis.

Milk urea nitrogen variation explained by differences in urea transport into the gastrointestinal tract in lactating dairy cows

Milk urea nitrogen (MUN) and blood urea nitrogen are correlated with nitrogen balance and nitrogen excretion; however, there is also a genetic component to MUN concentrations that could be associated with differences in urea transport. It was hypothesized that a portion of the variation in MUN concentrations among cows is caused by variation in gastrointestinal and kidney urea clearance rates. Eight lactating cows with varying MUN concentrations while fed a common diet were infused with [15N15N]urea to determine urea N entry rate (UER), gastrointestinal entry rate, returned to ornithine cycle, urea N used for anabolism, urea N excretion in feces and urine. Urea clearance rates by the kidneys and gastrointestinal tract were calculated from isotopic enrichment of urea excretion in urine and gut entry rate, respectively, and plasma urea N concentrations (PUN). Over the course of the experiment, animals weighed an average of 506 ± 62 kg and produced 26.3 ± 4.39 kg of milk/d, with MUN concentrations ranging from 11.6 to 17.3 mg/dL (average of 14.9 ± 2.1 mg/dL). Plasma urea N was positively correlated with UER, urea N excretion in urine, and urea N used for anabolism. Plasma urea N and MUN were negatively correlated with gut clearance rates and ratio of gastrointestinal entry rate to UER. This relationship supports the hypothesis that differences in gut urea transport activity among animals causes variation in PUN and MUN concentrations, and that cows with high PUN and MUN are less efficient at recycling PUN to the gastrointestinal tract and thus may be more susceptible to ruminal N deficiencies when fed low RDP diets. Such biological variation in urea metabolism necessitates an adequate safety margin when setting regulations for maximal MUN levels as an indicator of herd N efficiency.

Progress in the regulation of energy metabolic homeostasis by the SWI/SNF complex subunit Baf60a

Metabolic syndrome is a global chronic epidemic. Its pathogenesis is determined by genetic and environmental factors. Epigenetic modification is reported to regulate gene expression without altering its nucleotide sequences. In recent years, epigenetic modification is sensitively responded to environmental signals, further affecting the gene expression and signaling transduction. Among these regulators, chromatin remodeling SWI/SNF (SWItch/Sucrose non fermentable, SWI/SNF) complex subunit Baf60a plays an important role in maintaining energy homeostasis in mammals. In this paper, we described the pathophysiological roles of Baf60a in maintaining the balance of energy metabolism, including lipid metabolism, cholesterol metabolism, urea metabolism, as well as their rhythmicity. Therefore, in-depth understanding of Baf60a-orchestrated transcriptional network of energy metabolism will provide potential therapeutic targets and reliable theoretical supports for the treatment of metabolic syndrome.

RUMINAL AMMONIA AND BLOOD UREA METABOLISM IN SHEEP FED HAY WITH OR WITHOUT CONCENTRATE SUPPLEMENT

Metabolism of ruminal ammonia and blood urea was investigated in West African Dwarf ewes and wethers, fed a low quality hay with or without concentrate supplementation, using single injection of [15N] ammonium chloride (HN4Cl) or [15N] urea into the rumen and blood respectively. The percentages of 15N administered intraruminal as HN4Cl recovered in the urine, faeces and milk of the ewes were 4.3, 9.0 and 3.1, Also 32.3 and 28.7% of [15Nl urea administered into the blood were recovered in the urine of the wethers. Ruminal ammonia contributed 50.6% or protozoal-N in sheep fed hay and 14.2 78.7 and 35.0% respectively in sheep fed hay and concentrate. Also, 59.0 and 7.9% of ruminal ammonia-N was derived from blood urea of sheep fed hay and hay plus concentrate respectively. The inclusion of concentrate in the diet increased the extent of ruminal bacteria protein synthesis but not that of the protozoa, However, the contributions of ruminal ammonia to blood urea synthesis and of blood urea to ruminal ammonia were Sharply decreased in the presence of the concentrate.

Effect of increasing dietary proportion of plantain on milk production and nitrogen use of grazing dairy cows in late lactation

Abstract Context Plantain has shown promise as a forage that can mitigate nitrogen (N) losses from farm systems, although adoption and regulation requires knowledge of the minimum amount of forage area or diet quantity to observe an effect. Aims A grazing study was conducted to evaluate the effect of offering increasing proportions of spatially adjacent plantain (PL) and perennial ryegrass–white clover (PRGWC) on milk production and N utilisation of dairy cows. Methods Forty-eight late lactating cows blocked into replicated (n = 3) groups of four cows were randomly allocated to one of the following four forage treatments based on percentage area of plantain: 0%, 15%, 30%, or 60%. Cows were allocated 25 kg DM/cow.day of forage above ground level daily on the basis of metabolisable energy requirements. Dry matter intake was estimated from the difference between pre- and post-grazing pasture mass, using a calibrated electronic rising-plate meter. Milk production was measured as yield and milk solids, while N use was estimated from total milk N excretion and spot subsamples of blood, urine and faeces. Key results Offering cows spatially adjacent strips of PL increased apparent dry matter intake compared with PRGWC pasture alone (16.4 vs 15.1 kg DM/cow.day, P = 0.027) and apparent metabolisable energy intake (203 vs 188 MJ/kg.cow.day, P < 0.001). Milk yield (16.1 kg/cow.day), milk solids production (1.6 kg/cow.day) and fat concentration (5.69%) were unaffected by the proportion of plantain in the diet. PL offered at 60% of the area increased milk protein concentration compared with PRGWC (4.65 vs 4.36%, P < 0.01). There was no treatment effect on total apparent N intake (563 g N/cow.day), N excretion in milk (113 g N/cow.day) and N-utilisation efficiency (20 g milk N/100 g N consumed). However, total milk urea, blood urea and urine urea N concentrations declined with increasing plantain in the diet, reflecting an influence on urea metabolism. Conclusions Offering plantain to grazing dairy cows did not improve milk yield or N-use efficiency, but influenced urea metabolism. Implications Sowing plantain in spatially separate strips within perennial ryegrass–white clover pastures is a useful option to achieve target levels of plantain in the diet and, in conjunction with other mitigation strategies, can be used to improve the sustainability of pastoral dairy farming.

Whole exome sequencing make a definitive diagnosis of a Vietnamese patient with a late onset urea cycle disorder

Our report describes a female presenting with vomiting, fever, coma and right hemiplegia at 26 months of age. Biochemical tests revealed hyperammonemia, hyperlactatemia, elevated glutamine level, elevated transaminase and disorder of prothrombin time. She was priory diagnosed with urea cycle disorders (UCDs). UCDs are caused by mutations in eight genes that regulate the synthesis of enzymes and cofactors involved in urea metabolism. Singleton whole exome sequencing was applied to screen causative variants in these genes in the patient at 6 years of age. The result showed one heterozygous stop loss mutation c.1065A>G in the OTC gene as a potential disease causing in the patient. The mutation c.1065A>G leads to alternation of stop codon to tryptophan, resulting in elongation of fourteen amino acids in ornithine transcarbamylase (OTC) protein (p.Ter355TrpextTer14). Sanger sequencing in the family revealed the mutation c.1065A>G was not present in healthy parents and brother. Therefore, this mutation is considered as a de novo mutation in the patient. The mutation c.1065A>G was conferred to pathogenic according to the standards and guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology with 1 strong (PS2), 3 moderate (PM2, PM4 and PM5) and 1 support criteria (PP2). Although OTC deficiency is an X-linked recessive inheritance, approximately 15% of females carrying heterozygous variants showed the late onset OTC deficiency. Therefore, in combination of clinical presentations, laboratory findings and molecular genetic analyses, we made a definitive diagnosis of the patient with late onset OTC deficiency, a disorder of UCDs.

Differences between Holstein dairy cows in renal clearance rate of urea affect milk urea concentration and the relationship between milk urea and urinary nitrogen excretion

Urine and fecal excretions from cattle contribute to global nitrogen (N) emissions. The milk urea nitrogen (MUN) concentration in dairy cows is positively correlated with urinary urea N (UUN) emissions, and both decline with the reduction in crude protein intake. However, MUN concentration may differ between individual cows despite feeding the same ration. Thus, we hypothesized that due to differences in endogenous N utilization cows with high MUN concentration excrete more UUN than cows with a low MUN concentration. The objective of the present study was to elucidate N partitioning and urea metabolism in dairy cows with divergent MUN concentrations fed two planes of crude protein. Twenty Holstein dairy cows with high (HMU; n = 10) and low (LMU; n = 10) milk urea concentrations were fed two isocaloric diets with a low (LP) and normal (NP) crude protein level. Methane and ammonia emissions were recorded in respiration chambers. Feed intake, feces and urine excretions and milk yield were recorded for four days and subsamples were analyzed for total N and N-metabolites. A carbon-13 labeled urea bolus was administered intravenously followed by a series of plasma samplings. Total N and UUN excretions and ammonia emissions from excreta were lower on the LP diet, however, methane emissions, urinary N excretions and ammonia emissions were comparable between groups. Although plasma and salivary urea concentrations, urea pool size and urea turnover were higher, HMU cows had lower renal urea clearance rates. Additionally, HMU cows had lower renal clearance rates for creatinine, uric acid and creatine and excreted less uric acid (on the LP diet only) and creatine with urine. In conclusion, contrary to our hypothesis, HMU cows did not excrete more UUN than LMU cows. The lower urinary creatine excretion of HMU cows suggests that these animals have a lower environmental nitrogen footprint.

Lifestyle adaptations of Rhizobium from rhizosphere to symbiosis

By analyzing successive lifestyle stages of a model Rhizobium-legume symbiosis using mariner-based transposon insertion sequencing (INSeq), we have defined the genes required for rhizosphere growth, root colonization, bacterial infection, N2-fixing bacteroids, and release from legume (pea) nodules. While only 27 genes are annotated as nif and fix in Rhizobium leguminosarum, we show 603 genetic regions (593 genes, 5 transfer RNAs, and 5 RNA features) are required for the competitive ability to nodulate pea and fix N2 Of these, 146 are common to rhizosphere growth through to bacteroids. This large number of genes, defined as rhizosphere-progressive, highlights how critical successful competition in the rhizosphere is to subsequent infection and nodulation. As expected, there is also a large group (211) specific for nodule bacteria and bacteroid function. Nodule infection and bacteroid formation require genes for motility, cell envelope restructuring, nodulation signaling, N2 fixation, and metabolic adaptation. Metabolic adaptation includes urea, erythritol and aldehyde metabolism, glycogen synthesis, dicarboxylate metabolism, and glutamine synthesis (GlnII). There are 17 separate lifestyle adaptations specific to rhizosphere growth and 23 to root colonization, distinct from infection and nodule formation. These results dramatically highlight the importance of competition at multiple stages of a Rhizobium-legume symbiosis.

Chinese Yellow Rice Wine Processing with Reduced Ethyl Carbamate Formation by Deleting Transcriptional Regulator Dal80p in Saccharomyces cerevisiae.

Ethyl carbamate (EC) is a potential carcinogen that forms spontaneously during Chinese rice wine fermentation. The primary precursor for EC formation is urea, which originates from both external sources and arginine degradation. Urea degradation is suppressed by nitrogen catabolite repression (NCR) in Saccharomyces cerevisiae. The regulation of NCR is mediated by two positive regulators (Gln3p, Gat1p/Nil1p) and two negative regulators (Dal80p/Uga43p, Deh1p/Nil2p/GZF3p). DAL80 revealed higher transcriptional level when yeast cells were cultivated under nitrogen-limited conditions. In this study, when DAL80-deleted yeast cells were compared to wild-type BY4741 cells, less urea was accumulated, and genes involved in urea utilization were up-regulated. Furthermore, Chinese rice wine fermentation was conducted using dal80Δ cells; the concentrations of urea and EC were both reduced when compared to the BY4741 and traditional fermentation starter. The findings of this work indicated Dal80p is involved in EC formation possibly through regulating urea metabolism and may be used as the potential target for EC reduction.

Solving the Conundrum: Widespread Proteins Annotated for Urea Metabolism in Bacteria Are Carboxyguanidine Deiminases Mediating Nitrogen Assimilation from Guanidine.

Free guanidine is increasingly recognized as a relevant molecule in biological systems. Recently, it was reported that urea carboxylase acts preferentially on guanidine, and consequently, it was considered to participate directly in guanidine biodegradation. Urea carboxylase combines with allophanate hydrolase to comprise the activity of urea amidolyase, an enzyme predominantly found in bacteria and fungi that catalyzes the carboxylation and subsequent hydrolysis of urea to ammonia and carbon dioxide. Here, we demonstrate that urea carboxylase and allophanate hydrolase from Pseudomonas syringae are insufficient to catalyze the decomposition of guanidine. Rather, guanidine is decomposed to ammonia through the combined activities of urea carboxylase, allophanate hydrolase, and two additional proteins of the DUF1989 protein family, expansively annotated as urea carboxylase-associated family proteins. These proteins comprise the subunits of a heterodimeric carboxyguanidine deiminase (CgdAB), which hydrolyzes carboxyguanidine to N-carboxyurea (allophanate). The genes encoding CgdAB colocalize with genes encoding urea carboxylase and allophanate hydrolase. However, 25% of urea carboxylase genes, including all fungal urea amidolyases, do not colocalize with cgdAB. This subset of urea carboxylases correlates with a notable Asp to Asn mutation in the carboxyltransferase active site. Consistent with this observation, we demonstrate that fungal urea amidolyase retains a strong substrate preference for urea. The combined activities of urea carboxylase, carboxyguanidine deiminase and allophanate hydrolase represent a newly recognized pathway for the biodegradation of guanidine. These findings reinforce the relevance of guanidine as a biological metabolite and reveal a broadly distributed group of enzymes that act on guanidine in bacteria.

A mechanobiological mathematical model of liver metabolism

The liver plays a complex role in metabolism and detoxification, and better tools are needed to understand its function and to develop liver-targeted therapies. In this study, we establish a mechanobiological model of liver transport and hepatocyte biology to elucidate the metabolism of urea and albumin, the production/detoxification of ammonia, and consumption of oxygen and nutrients. Since hepatocellular shear stress (SS) can influence the enzymatic activities of liver, the effect of SS on the urea and albumin synthesis are empirically modeled through the mechanotransduction mechanisms. The results demonstrate that the rheology and dynamics of the sinusoid flow can significantly affect liver metabolism. We show that perfusate rheology and blood hematocrit can affect urea and albumin production by changing hepatocyte mechanosensitive metabolism. The model can also simulate enzymatic diseases of the liver such as hyperammonemia I, hyperammonemia II, hyperarginemia, citrollinemia, and argininosuccinicaciduria, which disrupt the urea metabolism and ammonia detoxification. The model is also able to predict how aggregate cultures of hepatocytes differ from single cell cultures. We conclude that in vitro perfusable devices for the study of liver metabolism or personalized medicine should be designed with similar morphology and fluid dynamics as patient liver tissue. This robust model can be adapted to any type of hepatocyte culture to determine how hepatocyte viability, functionality, and metabolism are influenced by liver pathologies and environmental conditions.

Codium fragile Ameliorates High-Fat Diet-Induced Metabolism by Modulating the Gut Microbiota in Mice.

Codium fragile (CF) is a functional seaweed food that has been used for its health effects, including immunostimulatory, anti-inflammatory, anti-obesity and anti-cancer activities, but the effect of CF extracts on obesity via regulation of intestinal microflora is still unknown. This study investigated anti-obesity effects of CF extracts on gut microbiota of diet-induced obese mice. C57BL/6 mice fed a high-fat (HF) diet were given CF extracts intragastrically for 12 weeks. CF extracts significantly decreased animal body weight and the size of adipocytes, while reducing serum levels of cholesterol and glucose. In addition, CF extracts significantly shifted the gut microbiota of mice by increasing the abundance of Bacteroidetes and decreasing the abundance of Verrucomicrobia species, in which the portion of beneficial bacteria (i.e., Ruminococcaceae, Lachnospiraceae and Acetatifactor) were increased. This resulted in shifting predicted intestinal metabolic pathways involved in regulating adipocytes (i.e., mevalonate metabolism), energy harvest (i.e., pyruvate fermentation and glycolysis), appetite (i.e., chorismate biosynthesis) and metabolic disorders (i.e., isoprene biosynthesis, urea metabolism, and peptidoglycan biosynthesis). In conclusion, our study showed that CF extracts ameliorate intestinal metabolism in HF-induced obese mice by modulating the gut microbiota.

Effect of salinity acclimation on osmoregulation, oxidative stress, and metabolic enzymes in the invasive Xenopus laevis.

Aquatic animals often display physiological adjustments to improve their biological performance and hydrosaline balance in saline environments. In addition to energetic costs associated with osmoregulation, oxidative stress, and the activation of the antioxidant system are common cellular responses to salt stress in many species, but the knowledge of osmoregulation-linked oxidative homeostasis in amphibians is scarce. Here we studied the biochemical responses and oxidative responses of Xenopus laevis females exposed for 40 days to two contrasting salinities: hypo-osmotic (150 mOsm·kg-1 ·H2 O NaCl, HYPO group) and hyper-osmotic environments (340 mOsm·kg-1 ·H2 O NaCl, HYPER group). We found an increase of plasma osmolality and plasma urea concentration in the animals incubated in the HYPER treatment. Increases in electrolyte concentration were paralleled with an increase of both citrate synthase and cytochrome c oxidase activities in liver and heart. Interestingly, HYPO group had higher catabolic activity of the skin and liver total antioxidant capacity (TAC), compared with animals from the HYPER group. Moreover, there was an inverse relationship between liver TAC and plasma osmolality; and with the metabolic enzymes from liver. These findings suggest that salinity induces changes in urea metabolism and specific activity of metabolic enzymes, which appears to be tissue-dependent in X. laevis. Contrary to our expectations, we also found a moderate change in the oxidative status as revealed by the increase in TAC activity in the animals acclimated to low salinity medium, but constancy in the lipid peroxidation of membranes.

Effects of urea on cell growth and physiological response in pigment biosynthesis in mixotrophic Chromochloris zofingiensis

The mixotrophic cultivation of Chromochloris zofingiensis (Chlorophyta, Trebouxiophyceae) under various urea concentrations was investigated for biomass and pigment production. The results showed that urea was favorable for biomass production with the highest biomass concentration of 8.86 g L−1 at 3.81 mmol L−1 of urea. When urea concentration was lowered to 0.19 mmol L−1, the highest content (0.99 mg g−1) and yield (4.11 mg L−1) of total carotenoids was reached due to an extremely high C/N ratio. Principle component analysis revealed that urea concentrations could indeed affect biomass production and pigment biosynthesis involving intracellular nitrogen assimilation and catabolism associated with chloroplast degradation. Our present study evaluates the feasibility of using urea for C. zofingiensis cultivation and provides new insights for a better understanding of the close relationships between urea metabolism and pigment biosynthesis in mixotrophic C. zofingiensis.

Metabolomic identification of placental alterations in fetal growth restriction

Introduction Fetal growth restriction (FGR), viz., birth weight <10th percentile is a common pregnancy complication which increases the risk of adverse fetal and newborn outcomes. The placenta is the key organ for fetal growth as it controls oxygen and nutrient availability. This study aims to elucidate the mechanisms of and identify putative placental biomarkers for FGR using high-resolution metabolomics. Methods Placenta samples from 19 FGR cases and 30 controls were analyzed using proton magnetic resonance (1H NMR) spectroscopy and direct flow injection mass spectrometry with reverse-phase liquid-chromatography mass spectrometry (DI-LC-MS/MS). Significant concentration differences (p-value <.05) in 179 of the 220 metabolites were measured. Results Of the 179 metabolites, 176 (98.3%) had reduced placental levels in FGR cases. The best performing metabolite model: 3-hydroxybutyrate, glycine and PCaaC42:0 achieved an AUC (95% CI) = 0.912 (0.814–1.000) with a sensitivity of 86.7% and specificity of 84.2% for FGR detection. Metabolite set enrichment analysis (MSEA) revealed significant (p < .05) perturbation of multiple placental metabolite pathways including urea metabolism, ammonia recycling, porphyrin metabolism, bile acid biosynthesis, galactose metabolism and perturbed protein biosynthesis. Conclusion The placental metabolic pathway analysis revealed abnormalities that are consistent with fetal hepatic dysfunction in FGR. Near global reduction of metabolite concentrations was found in the placenta from FGR cases and metabolites demonstrated excellent diagnostic accuracy for FGR detection.

Role of the Dihydrodipicolinate Synthase DapA1 on Iron Homeostasis During Cyanide Assimilation by the Alkaliphilic Bacterium Pseudomonas pseudoalcaligenes CECT5344.

Cyanide is a toxic compound widely used in mining and jewelry industries, as well as in the synthesis of many different chemicals. Cyanide toxicity derives from its high affinity for metals, which causes inhibition of relevant metalloenzymes. However, some cyanide-degrading microorganisms like the alkaliphilic bacterium Pseudomonas pseudoalcaligenes CECT5344 may detoxify hazardous industrial wastewaters that contain elevated cyanide and metal concentrations. Considering that iron availability is strongly reduced in the presence of cyanide, mechanisms for iron homeostasis should be required for cyanide biodegradation. Previous omic studies revealed that in the presence of a cyanide-containing jewelry residue the strain CECT5344 overproduced the dihydrodipicolinate synthase DapA1, a protein involved in lysine metabolism that also participates in the synthesis of dipicolinates, which are excellent metal chelators. In this work, a dapA1– mutant of P. pseudoalcaligenes CECT5344 has been generated and characterized. This mutant showed reduced growth and cyanide consumption in media with the cyanide-containing wastewater. Intracellular levels of metals like iron, copper and zinc were increased in the dapA1– mutant, especially in cells grown with the jewelry residue. In addition, a differential quantitative proteomic analysis by LC-MS/MS was carried out between the wild-type and the dapA1– mutant strains in media with jewelry residue. The mutation in the dapA1 gene altered the expression of several proteins related to urea cycle and metabolism of arginine and other amino acids. Additionally, the dapA1– mutant showed increased levels of the global nitrogen regulator PII and the glutamine synthetase. This proteomic study has also highlighted that the DapA1 protein is relevant for cyanide resistance, oxidative stress and iron homeostasis response, which is mediated by the ferric uptake regulator Fur. DapA1 is required to produce dipicolinates that could act as iron chelators, conferring protection against oxidative stress and allowing the regeneration of Fe-S centers to reactivate cyanide-damaged metalloproteins.

Advances in Studies on Effects of Nitrogen Metabolism Pathways on Seed Germination and Seedling Growth of Plants

Nitrogen is an important component of plant nucleic acids, proteins and chlorophyll. It is an essential nutrient element required for the plant growth and development. It is also one of the important factors limiting the growth of plants. This review introduces several important aspects of nitrogen metabolism including arginine metabolism, urea metabolism pathway and glutamine synthetase assimilation process, and also induces and summarizes the response mechanisms of nitrogen metabolism on the seed germination and seedling growth. In addition, it also importantly summarizes the research advances in the effects of the nitrogen metabolism on seed germination and seedling growth of plants. At the same time, this review briefly summarizes the application values of nitrogen in crop production, environmental pollution and ecological conditions and so on, and also discusses the limitations and deficiencies of nitrogen metabolism research, providing the certain theoretical foundations for the research of the effects of nitrogen metabolism pathway on the seed germination and seedling growth of plants.