Inborn Errors of RNA Lariat Metabolism in Humans with Brainstem Viral Infection

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Nitrogen Metabolism in Soybean Tissue Culture: II. Urea Utilization and Urease Synthesis Require Ni

Potassium citrate (10 mM, pH 6) inhibits the growth of cultured (Glycine max L.) cells when urea is the sole nitrogen source. Ureadependent citrate toxicity is overcome by three separate additions to the growth medium: (a) NH₄Cl (20 mM); (b) high levels of MgCl₂ (10 mM) or CaCl₂ (5-10 mM); (c) low levels of NiSO₄ (10⁻² mM). Additions of 10⁻² mM NiSO₄ not only overcome citrate growth inhibition but the resultant growth is usually better than urea-supported growth in basal medium (neither added citrate nor added nickel). In the absence of added citrate, exceedingly low levels of NiSO₄ (10⁻⁴ mM) strongly stimulate urea-supported growth in suspension cultures.     

Inborn Errors of Purine and Pyrimidine Metabolism: How Much We Owe to H. Anne Simmonds

Purines and pyrimidines, regarded for a long time merely as building blocks for nucleic acid synthesis and intermediates in the transfer of metabolic energy, have attracted increasing attention after genetically determined aberrations in their metabolism were linked to a range of symptoms from hyperuricemia and immunodeficiency to neurological disorders. The pathogenesis of such disorders involves cell or mitochondrial damage, but the molecular mechanisms underlying symptoms is often unclear. H. Anne Simmonds made major contributions to the metabolic, clinical, and molecular aspects of these disorders and the Purine Research Laboratory, which she established in London, became the world center for clinical and experimental studies in the field. We owe her gratitude not only for this direct contribution but also for her enthusiasm for purine and pyrimidine research that she transmitted to generations of scientists. Our research in this field stemmed from expertise in pyridine metabolism and its connection with purines, and from clinical involvement with biochemical diagnosis of enzyme deficiencies. We joined H. Anne Simmonds in studying the biochemical basis of altered NAD content in erythrocytes of PNP- and HPRT-deficient patients, discovering some alterations in NAD synthesis and breakdown.     

COVID-19 impact on the diagnosis of Inborn Errors of Metabolism: Data from a reference center in Brazil

The COVID-19 pandemic led to the reorganization of health care in several countries, including Brazil. Inborn Errors of Metabolism (IEM) are a group of rare and difficult to diagnose genetic diseases caused by pathogenic variants in genes that code for enzymes, cofactors, or structural proteins affecting different metabolic pathways. The aim of this study was to evaluate how COVID-19 affected the diagnosis of patients with IEM during the first year of the pandemic in Brazil comparing two distinct periods: from March 1^st, 2019 to February 29^th, 2020 (TIME A) and from March 1^st, 2020 to February 28^th, 2021 (TIME B), by the analysis of the number of tests and diagnoses performed in a Reference Center in South of Brazil. In the comparison TIME A with TIME B, we observe a reduction in the total number of tests performed (46%) and in the number of diagnoses (34%). In both periods analyzed, mucopolysaccharidoses (all subtypes combined) was the most frequent LD suspected and/or confirmed. Our data indicates a large reduction in the number of tests requested for the investigation of IEM and consequently a large reduction in the number of diagnoses caused by the COVID-19 pandemic leading to a significant underdiagnosis of IEM.     

Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease

ObjectivesThe extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort.MethodsBone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6–18 years with an estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73m². 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group.ResultsStandardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score.ConclusionMarkers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity.     

Effcts of Blue Light and Ammonia on Nitrogen Metabolism in a Colorless Mutant of Chlorella

Illumination of a colorless mutant of Chlorella vulgaris 1lh(M125) with blue light enhanced both the uptake of nitrate andthe release of ammonia. These effects were not observed underillumination with red light. The release of ammonia was alsoenhanced by the addition of methionine sulphoximine (MSX), aninhibitor of glutamine synthetase (GS). Addition of MSX to culturesin the dark increased the rate of breakdown of starch. Algal cells grown in nitrate-containing medium did not showthe aminating activity of glutamate dehydrogenase (GDH). Additionof large (millimolar) amounts of ammonia in the dark resultedin the induction of NADPH-GDH activity and, in addition, a decreasein GS activity. From these results it appears that GS catalyzesthe primary step in the assimilation of ammonia in algal cellsgrown in nitrate-containing medium. Two isoforms (GS1 and GS2)of GS have been separated by ion exchange chromatography. Theactivities of both isoforms were decreased upon the additionof ammonia. Illumination of the alga with blue light at intensities up to10,000 mW m^–2 enhanced the measurable activity of GS invitro, while higher intensities were ineffective. In red lightno such effect was observed. The effects of blue light and ammonia on nitrogen metabolismin algal cells are discussed. (Received November 25, 1988; Accepted March 6, 1989)     

Effect of Ammonia Concentration on the Composition, Hydrolytic Activity and Nitrogen Metabolism of the Microbial Flora of the Rumen

The mean NH₃ concentration in the rumen of sheep fed whole barley (08 kg/d) by continuous feeders was increased from 61 to 134 HIM by supplementing the feed with urea (30 g/kg). This change caused a 90% increase in the rate of degradation of rolled barley, and smaller increases in the rates of degradation of protein and plant fibre in the rumen. The total viable count and numbers of pectinolytic bacteria in rumen fluid increased with the urea supplement. Enzyme studies indicated that NAD-linked glutamate dehydrogenase was the main pathway of NH₃ assimilation by rumen bacteria at both NH₃ concentrations. Glutamate was the main free amino acid found in the rumen at low NH₃ but, despite the low activity of alanine dehydrogenase and glutamate-pyruvate aminotransferase, alanine was the principal amino acid at high NH₃ concentrations. Hydrolytic rumen bacteria may require the higher NH₃ concentration either for effective NH₃ assimilation by an unknown mechanism involving alanine or for full expression of enzyme activity.     

Nitrogen Metabolism in Plant Cell Suspension Cultures: II. Role of Organic Acids during Growth on Ammonia

Tobacco cells (Nicotiana tabacum) are capable of growth on ammonia as a sole nitrogen source only when succinate, malate, fumarate, citrate, α-ketoglutarate, glutamate, or pyruvate is added to the growth medium. A ratio between the molar concentrations of ammonia to succinate (as a complementary organic acid) in the growth medium of 1.5 was optimal. Succinate had no effect on the rate of uptake of ammonia from the medium into the cells although it did affect the intracellular concentration of ammonia. However, the changes were not sufficient to explain inhibition of growth as being due to ammonia toxicity. The radioactivity from ¹⁴C-succinate was incorporated into malate, glutamate, and aspartate within 2 minutes.     

氮肥对2个杨树品种碳氮代谢的影响

研究以‘丹红’杨(美洲黑杨)和‘通辽1号’杨(小叶杨)为材料,在田间进行施氮肥和不施氮肥处理,分析2个杨树品种的生长性状、碳氮相关代谢物和发育木质部转录组的变化特征,探讨不同杨树品种氮肥利用的生理机制,为杨树的氮高效利用遗传育种奠定基础。结果表明:(1)‘丹红’杨和‘通辽1号’杨的总生物量在施氮处理后分别比不施氮处理提高了1.69倍和1.10倍;‘丹红’杨的总生物量在施氮肥和不施氮肥条件下分别是‘通辽1号’杨的13倍和10倍。(2)施氮处理显著抑制‘丹红’杨和‘通辽1号’杨树皮和木质部中总氮和多种水解氨基酸的含量,但是没有明显影响木质部的总碳、纤维素、半纤维素和木质素含量。(3)施氮处理显著影响了2个杨树品种发育木质部碳固定、糖代谢、氨基酸合成等碳氮代谢途径的基因的高表达,从而促进了植株生物量的积累。研究发现,施氮处理可以显著促进杨树发育木质部碳氮代谢途径相关基因的高表达,从而促进了杨树生物量的积累和生长;‘丹红’杨的木材产量在不同的氮素环境下都远远高于‘通辽1号’杨,更加适合人工林的大面积推广和种植。     

Effect of Chronic Lead Ingestion by Rats on Glucose Metabolism and Acetylcholine Synthesis in Cerebral Cortex Slices

Abstract: The effect of chronic low-level lead (Pb²⁺) ingestion on the metabolic pathways leading to the acetyl moiety of acetylcholine (ACh) was examined. Cerebral cortex slices, prepared from untreated or Pb²⁺-exposed rats (600 ppm lead acetate in the drinking water for 20 days), were incubated in Krebs-Ringer bicarbonate buffer with 10 m M glucose and tracer amounts of [6-³H]glucose and either [6-¹⁴C]glucose or [3-¹⁴C] β -hydroxybutyrate. Altering the concentration of Pb²⁺ in the drinking water produced a dose-related increase in blood and brain lead levels. When tissue from Pb²⁺-exposed rats was incubated with mixed-labeled glucose, incorporation into lacate, citrate, and ACh was considerably decreased, although no changes occurred in the ³H/¹⁴C ratios. Similar effects of Pb²⁺ were found when ¹⁴C-labeled β -hydroxy-butyrate was substituted for the [¹⁴C]glucose. It appears from these data that Pb²⁺ exerts a generalized effect on energy metabolism and not on a specific step in glucose metabolism. The impairment of glucose metabolism may explain partially the Pb²⁺-induced changes observed in cholinergic function.     

氮素形态对铁线莲光合特性及氮代谢的影响

为了解铁线莲的光合性能和氮素代谢的响应机制,对不同氮素形态配比下1 a生厚叶铁线莲(Clematis crassifolia)与天台铁线莲(C.paten ssp.tientaiensis)的生长、光响应曲线、A-Ci曲线和氮代谢相关酶活性进行了比较.结果表明,氮素形态配比显著影响铁线莲的生物量和叶绿素(Chl)含量,...     

In Situ Nitrogen Mineralization,Nitrification, and Ammonia Volatilization in Maize Field Fertilized with Urea in Huanghuaihai Region of Northern China

Nitrogen (N) fertilization potentially affects soil N mineralization and leaching, and can enhance NH₃ volatilization, thus impacting crop production. A fertilizer experiment with five levels of N addition (0, 79, 147, 215 and 375 kg N ha^-1) was performed in 2009 and 2010 in a maize field in Huanghuaihai region, China, where > 300 kg N ha^-1 has been routinely applied to soil during maize growth period of 120 days. Responses of net N mineralization, inorganic N flux (0–10cm), NH₃ volatilization, and maize yield to N fertilization were measured. During the growth period, net N mineralization and nitrification varied seasonally, with higher rates occurring in August and coinciding with the R1 stage of maize growth. Soil NO₃ ⁻-N contributed to more than 60% of inorganic N flux during maize growth. Cumulative NH₃ volatilization increased with N additions, with total NH₃ volatilization during maize growth accounting for about 4% of added N. Relative to the control, mean maize yield in the fertilizer treatments increased by 17% and 20% in 2009 and 2010, respectively. However, grain yield, aboveground biomass, and plant N accumulation did not increase with added N at levels > 215 kg N ha^-1. These results suggest that the current N rate of 300 kg N ha^-1 is not only excessive, but also reduces fertilizer efficacy and may contribute to environmental problems such as global warming and eutrophication of ground water and streams.     

Studies on the Reduction of Terpenes with Sodium in Aqueous Ammonia

The reduction of p-mentha-1,3-dien-7-al (II) with sodium in aqueous ammonia afforded trans- and cis-p-menthan-7-ol via 1-p-menthen-7-al (phellandral) and trans- and cis-p-menthan-7-al, respectively, in which the trans forms were obtained predominantly due to the stereoelectronic requirement.     

The Effect of Molybdenum upon the Nitrogen Metabolism of Anabaena cylindrica: I. A Study of the Molybdenum Requirement for Nitrogen Fixation and for Nitrate and Ammonia Assimilation

The effect of molybdenum concentration upon the growth of Anabaenacylindrica is studied. Within the range of molybdenum concentrationthat it was found possible to achieve by the methods described,the element does not affect growth on ammonium chloride, butit is required for healthy growth on nitrate or gaseous nitrogen,the optimal concentrations being about 0·075 and 0·20p.p.m., respectively. Molybdenum appears to be unnecessary fornitrate uptake.     

Effect of Salinity and Potassium on the Uptake of Nitrogen and on Nitrogen Metabolism in Young Barley Plants

In a solution culture experiment with 4-week-old barley plants (variety Villa) the influence of NaCl salinization and of KCl additions on the uptake and turnover of labelled N (¹⁵NH₄¹⁵NO₃) was studied. Labelled N was applied for 24 h at the end of the growth period. Salinization impaired growth and uptake of labelled N. The incorporation of labelled N into the protein fraction, however, was improved by NaCl salinization. Additions of KCl to the nutrient solution diminished the negative effect of NaCl salinization on growth. At both NaCl salinization levels (60 and 120 mM) K additions favoured the uptake of labelled N and particularly its incorporation into the protein fraction. It is suggested that the negative influence of the NaCl stress is not primarily due to an impaired protein synthesis, but is possibly caused by a deterimental effect of Na on other metabolic processes.     

Studies on the Reduction of Terpenes with Sodium in Aqueous Ammonia

The reduction of (?)-perillaldehyde (I) with sodium in aqueous ammonia afforded mainly trans- and cis-dihydroperillylalcohols (III_a and III_b). This fact indicates that this reduction method can surely be applied to α,β-unsaturated monoterpene aldehydes which are extremely sensitive to alkali and that the unconjugated carbon-carbon double bond is normally inert to this reducing condition.