Structure of putative tumor suppressor ALDH1L1

Putative tumor suppressor ALDH1L1, the product of natural fusion of three unrelated genes, regulates folate metabolism by catalyzing NADP+-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO2. Cryo-EM structures of tetrameric rat ALDH1L1 revealed the architecture and functional domain interactions of this complex enzyme. Highly mobile N-terminal domains, which remove formyl from 10-formyltetrahydrofolate, undergo multiple transient inter-domain interactions. The C-terminal aldehyde dehydrogenase domains, which convert formyl to CO2, form unusually large interfaces with the intermediate domains, homologs of acyl/peptidyl carrier proteins (A/PCPs), which transfer the formyl group between the catalytic domains. The 4′-phosphopantetheine arm of the intermediate domain is fully extended and reaches deep into the catalytic pocket of the C-terminal domain. Remarkably, the tetrameric state of ALDH1L1 is indispensable for catalysis because the intermediate domain transfers formyl between the catalytic domains of different protomers. These findings emphasize the versatility of A/PCPs in complex, highly dynamic enzymatic systems.

Monovalent Copper Ions Inhibit Enzymatic Systems

The effect of monovalent copper ions on enzymatic systems has hardly been studied to date; this is due to the low stability of monovalent copper ions in aqueous solutions, which led to the assumption that their concentration is negligible in biological systems. However, in an anaerobic atmosphere, and in the presence of a ligand that stabilizes the monovalent copper ions over the divalent copper ions, high and stable concentrations of monovalent copper ions can be reached. Moreover, the cell cytoplasm has a substantial concentration of potential stabilizers that can explain significant concentrations of monovalent copper ions in the cytoplasm. This study demonstrates the effect of monovalent and divalent copper ions on DNA polymerase, ligaseT4 DNA, the restriction enzymes EcoP15I and EcoR I, acid phosphatase, and α and βamylase enzymes. These systems were chosen because they can be monitored under conditions necessary for maintaining a stable concentration of monovalent copper ions, and since they exhibit a wide range of dependency on ATP. Previous studies indicated that ATP interacts with monovalent and divalent copper ions and stabilizing monovalent copper ions over divalent copper ions. The results showed that monovalent copper ions dramatically inhibit DNA polymerase and acid phosphatase, inhibit ligaseT4 DNA and the restriction enzyme EcoP15I, moderately inhibit α and β amylase, and have no effect on the restriction enzyme EcoR I. From the results presented in this work, it can be concluded that the mechanism is not one of oxidative stress, even though monovalent copper ions generate reactive oxygen species (ROS). Molecular oxygen in the medium, which is supposed to increase the oxidative stress, impairs the inhibitory effect of monovalent and divalent copper ions, and the kinetics of the inhibition is not suitable for the ROS mechanism.ATP forms a complex with copper ions (di and monovalent ions, where the latter is more stable) in which the metal ion is bound both to the nitrogen base and to the oxygen charged on the phosphate groups, forming an unusually distorted complex. The results of this study indicate that these complexes have the ability to inhibit enzymatic systems that are dependent on ATP.This finding can provide an explanation for the strong antimicrobial activity of monovalent copper ions, suggesting that rapid and lethal metabolic damage is the main mechanism of monovalent copper ions’ antimicrobial effect.

The activity of enzymes can be modified by homeopathic dilutions of their effectors

Introduction: The fungal and bacterial materials are very useful for testing the influence of low and very low doses of low molecular phenolic effectors on enzymatic system of phenoloxidases when they are incubated together in the reaction space. Aim: Searching for the model useful biological systems to study the action of diluted low molecular substances on living organisms, which is based on common physical and biochemical analytical procedures. Methods: The fungal and actinomycetal bacterial materials from laboratory cultures as a source of common phenoloxidases, laccase, peroxidase and O-demethylase as well as the pure plant peroxidase were used in experiments described earlier [1-5]. Subsequent dilutions of low molecular phenolic metabolites, appropriate for studied enzymatic systems, prepared in 75% ethanol in the proportion of 1:100 (centesimal) and dynamized by shaking in accordance with homeopathic procedures were prepared in our laboratory. During experiments with bacterial and fungal materials and a pure plant peroxidase, which were incubated together with subsequent dilutions of proper phenolic effector, different analytic methods were used including a gel (PAGE) [4] and capillary (MEKCE) electrophoresis [5], spectral and colorimetric methods [1,2,3] as well as the electron microscopy [5]. Results: In the light of presented data [1-5], the incubation of biological material with diluted phenolic effectors induces various effects on tested enzyme activity. It changed in sinusoidal manner with an gradual growth of dilution rate of tested effectors, which was distinctly visible on the diagram when the number of dilutions was localized on abscissa and biological activity on the ordinate. Exemplary results of the chosen experiments will be presented. For tested enzymes: laccase, peroxidase and O-demethylase, the distance between maximal points of enzymatic activity, shown on a sine curve, repeats more often every 10 subsequent centesimal dilutions. Along with the extension of incubation period the displacement of maximal and minimal points on curve were noticed, which revealed a dynamic aspect of studied phenomenon. Conclusions: Fungal and bacterial cells seem to be a very convenient material for studying the action of diluted metabolites on enzymatic systems because their popular presence in environment. Results of all experiments confirmed the same nature of the mentioned observations. Because other authors had similar conclusion concerning human [6,7] and plant materials [8,9], the described relations seem to be common in natural world. It could also be stressed that the therapeutic effect of homeopathic remedies could be based on the mechanism described above and it is highly probable that it leads to a normalisation of disturbed enzyme systems in the living organisms.

Impact of Anemia on the School Performance of Students at a Public School in Ceará

Anemia is defined as a condition in which hemoglobin levels are below the normal range. Among children and adolescents, iron deficiency is responsible for most cases. Iron is an essential compound for the production of red blood cells and transportation of oxygen, as well as for the integration of the enzymatic systems of different tissues. Patients with iron deficiency anemia may have impaired cognitive, physical and immune development, thus increasing the risk of infections and even death. This is a cross-sectional study to analyze the prevalence of anemia and its impact on school and nutritional performance among elementary school adolescents aged between 10 and 14 years from May 2019 to October 2019.

Apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients

Sepsis is a prevalent life-threatening condition related to a systemic infection, and with unresolved issues including refractory septic shock and organ failures. Endogenously released catecholamines are often inefficient to maintain blood pressure, and low reactivity to exogenous catecholamines with risk of sympathetic overstimulation is well documented in septic shock. In this context, apelinergics are efficient and safe inotrope and vasoregulator in rodents. However, their utility in a larger animal model as well as the limitations with regards to the enzymatic breakdown during sepsis, need to be investigated. The therapeutic potential and degradation of apelinergics in sepsis were tested experimentally and in a cohort of patients. (1) 36 sheep with or without fecal peritonitis-induced septic shock (a large animal experimental design aimed to mimic the human septic shock paradigm) were evaluated for hemodynamic and renal responsiveness to incremental doses of two dominant apelinergics: apelin-13 (APLN-13) or Elabela (ELA), and (2) 52 subjects (33 patients with sepsis/septic shock and 19 healthy volunteers) were investigated for early levels of endogenous apelinergics in the blood, the related enzymatic degradation profile, and data regarding sepsis outcome. APLN-13 was the only one apelinergic which efficiently improved hemodynamics in both healthy and septic sheep. Endogenous apelinergic levels early rose, and specific enzymatic breakdown activities potentially threatened endogenous apelin system reactivity and negatively impacted the outcome in human sepsis. Short-term exogenous APLN-13 infusion is helpful in stabilizing cardiorenal functions in ovine septic shock; however, this ability might be impaired by specific enzymatic systems triggered during the early time course of human sepsis. Strategies to improve resistance of APLN-13 to degradation and/or to overcome sepsis-induced enzymatic breakdown environment should guide future works.

Catalytic Methods for the Production of Sugar Esters

Nowadays, Sugar esters (SEs) have become the focus of researchers due to their biocompatibility and extensive industrial applications as surfactants. This trend provides new methods and opportunities for the development of green synthetic chemistry. Taking the above into consideration, a critical review presented in this work emphasized the efficiency of catalyzing the synthesis of SEs with minimal hazardous by-products. These catalytic media have been employed with various impacts involving chemical, biological, and other catalytic materials. Chemical methods have been reported to show limitations in terms of preparation and bio-compatibility. To solve these shortcomings, therefore, other technologies have been adopted; ionic liquids (eutectic solvents), chemo-enzymatic systems and chemo-enzymatic systems on a catalytic surface. The use of chemo-enzymatic systems on catalytic surfaces has proved to be suitable in solving biocompatibility and stability problems and correspondingly increasing the yield of esters formed. Therefore, finding an improved catalytic surface, and the sustainable optimal reaction conditions for enzymes will be vital to improving sugar ester conversion. This study highlights the different catalytic advances employed in the esterification of SEs.

The evaluation of the health risk in ice hockey players based on the predictors that characterize the tension of adaptive organism systems

Objective: to search for markers of health risk in ice hockey players by the blood parameters.Materials and methods: a total of 40 blood parameters (that characterize nutrient metabolism, humoral immunity, oxidative and nitrosative stress, the system of antioxidant protection) in hockey players with different body weights were evaluated 2.5, 4, and 6 months of the playing season (n = 39).Results: the levels of uric acid and creatinine indicated insufficient recreation of the organism after the games. Creatine phosphokinase­MB and AST indicated the influence on the cardiovascular muscle (verified by the De Ritis ratio). Dyslipidemia was the main factor of cardiovascular risk. Cortisol indicated the prevalence of catabolic processes and psychoemotional tension. The changes in the levels of immunoglobulins and C­reactive protein could result from a compensatory reaction of the organism to stress. The oxidized glutathione indicated the accumulation of products of lipid peroxidation and ongoing oxidative stress. The insufficiency in vitamins of groups B and E could decrease the effectiveness of enzymatic systems and enzymatic links of the oxidant system. The insufficiency of chrome could impair carbohydrate and fat metabolism.Conclusion: predictors for prenosological diagnostics of general health were established. They included urea, total cholesterol of high and low density, vitamin­mineral balance parameters, isoform of creatine kinase, aspartate aminotransferase, cortisol, and glutathione. Professional activity had the most negative influence on the health of sportsmen with lower body weight.

Model-Based Optimization of Mannitol Production by Using a Sequence of Batch Reactors for a Coupled Bi-Enzymatic Process—A Dynamic Approach

Multi-enzymatic reactions can successfully replace complex chemical syntheses, using milder reaction conditions, and generating less waste. The present model-based analysis compares the performances of several optimally operated Batch Reactors (BR) with those of an optimally operated serial Sequence of BRs (SeqBR). In multi-enzymatic systems, SeqBR could be more advantageous and flexible, allowing the optimization of costly enzymes amounts used in each BR in the series. Exemplification was made for the bi-enzymatic reduction of D-fructose to mannitol by using MDH (mannitol dehydrogenase) and the NADH cofactor, with the in situ continuous regeneration of NADH at the expense of formate degradation in the presence of FDH (formate dehydrogenase). For such coupled enzymatic systems, the model-based engineering evaluations are difficult tasks, because they must account for the common species’ initial levels, their interaction, and their dynamics. The determination of optimal operating modes of sole BR or of a SeqBR turns into a multi-objective optimization problem with multiple constraints to be solved for every particular system. The study presents multiple elements of novelty: (i) the proof of higher performances of an optimal SeqBR (including N-BRs) compared to a sole optimal BR operated for N-number of runs and (ii) the effect of using a multi-objective optimization criteria on SeqBR adjustable dynamics.

Methods of concentrated ingredients forms based on rowanberry (Sorbus aucuparia) producing

В данной работе исследована возможность концентрирования ингредиентов различного состава, полученных с применением ферментативных систем целевого назначения, на современных мембранных установках. Наработаны опытные образцы товарных форм ингредиентов из рябины сушеной. In this work, we investigated the possibility of concentrating ingredients of various compositions, obtained with the use of targeted enzymatic systems, in modern membrane installations. Prototypes of commercial forms of ingredients from dried mountain ash have been developed.