Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity

Substrate metabolite concentrations are inversely related to the in vivo capacity of their converting enzymes.Local metabolite responses represent a passive mechanism to achieve metabolic homeostasis upon perturbations in enzyme capacity.Enzyme capacity and metabolite concentration control the metabolic reaction rate

Metabolic landscape of the male mouse gut identifies different niches determined by microbial activities.

Distinct niches of the mammalian gut are populated by diverse microbiota, but the contribution of spatial variation to intestinal metabolism remains unclear. Here we present a map of the longitudinal metabolome along the gut of healthy colonized and germ-free male mice. With this map, we reveal a general shift from amino acids in the small intestine to organic acids, vitamins and nucleotides in the large intestine. We compare the metabolic landscapes in colonized versus germ-free mice to disentangle the origin of many metabolites in different niches, which in some cases allows us to infer the underlying processes or identify the producing species. Beyond the known impact of diet on the small intestinal metabolic niche, distinct spatial patterns suggest specific microbial influence on the metabolome in the small intestine. Thus, we present a map of intestinal metabolism and identify metabolite-microbe associations, which provide a basis to connect the spatial occurrence of bioactive compounds to host or microorganism metabolism

Перспективи використання культивованих грибів у технології ковбасних виробів

In order to solve the problems associated with expanding range of sausage meat component of high biological value, a search was conducted for alternative, natural and affordable sources of protein. Protein deficiency in human nutrition has led to the search for ways to increase biological value. It was proposed the optimal ratio of components of sausage meat, consisting of meat and mushroom raw materials. The purpose of this combination is to achieve the composition of sausages to the desired approximation of the "ideal protein" with the established technological effects for this production. The main objective of this work is to study the food and taste qualities of the finished product to expand the range of functional sausages at meat processing enterprises in Ukraine and China. Analysis of these data shows that an increase in the level of meat substitution with mushroom raw materials leads to a redistribution of the mass fractions of moisture, protein, fat and ash. The redistribution of these same indicators is affected by the physical state of the introduced mushroom raw material: powder or finely crushed mass. It was recorded a decrease in the mass fraction of fat by approximately 3% and 6%, respectively. Therefore, it was noted a decrease in energy value from 362 kcal to 335-304 kcal. The proportion of carbohydrates in the experimental samples has increased by an average of 1-2%. The mass fraction of protein remained almost unchanged, but the composition of the protein was closer to the "ideal protein". According to the results of organoleptic evaluation, it was found that when developing recipes for cooked smoked sausages, it is advisable to add boiled mushrooms in an amount of 15 - 20% in finely crushed form. It is advisable to add in the amount of 3.0 - 7.0% at the mixing stage in the form of a dry powder of fried mushrooms. The data presented in this article make it possible to assess the prospects of t he food industry in the production of sausages enriched with semi-finished products of varying degrees of readiness based on cultivated mushrooms. The results of the analytical study reflect the unique degree of the cultivated mushrooms amino acid composition approximation to the "ideal protein". Particular attention was paid to essential (limiting) amino acids and their content in new types of sausages.Для вирішення проблем, пов'язаних з розширенням асортименту ковбасних виробів підвищеної біологічної цінності, був проведений пошук альтернативних, природних і доступних джерел білка. Такими пропонується розглядати культивовані гриби. Дефіцит білка в раціон харчування людей, давно вже став причиною пошуку способів підвищення біологічної цінності, тому ми пропонуємо оптимальні співвідношення компонентів ковбасного фаршу, що складається з м'ясного та грибного сировини. Метою такого комбінування є досягнення складу ковбасних виробів до бажаного наближення до "ідеального білку" при встановлених технологічних ефектах для даного виробництва. Основним завданням роботи є вивчення харчових і смакових якостей готової продукції для розширення асортименту функціональних ковбасних виробів на м'ясопереробних підприємствах України і Китаю. Аналіз наведених даних показує, що зі збільшенням рівня заміни м'яса грибним сировиною проходить перерозподіл масових часток вологи, білка, жиру і зольності. На перерозподіл цих же показників впливає фізичний стан внесеного грибного сировини: порошок або тонко подрібнена маса. Було зафіксовано зменшення масової частки жиру приблизно на 3% і 6% відповідно. Отже, зниження енергетичної цінності: з 362 ккал до 335 - 304 ккал. Частка вуглеводів у дослідних зразках збільшувалася в середньому на 1-2%. Масова частка білка залишалася практично незмінною, але склад білка був ближчий до "ідеального білку". За результатами органолептичної оцінки з'ясовано, що при розробці рецептур варено-копчених ковбас доцільно вносити варені гриби в кількості 15 - 20% в тонкоподрібненому вигляді. У вигляді сухого порошку з обсмажених грибів - в кількості 3,0 - 7,0% на етапі перемішування. Наведені в статті дані, дозволяють оцінити перспективу напрямків харчової промисловості в сфері виробництва ковбасних виробів, збагачених напівфабрикатами різного ступеня готовності на основі культивованих грибів. Результати аналітичного дослідження, відображають унікальну ступінь наближення амінокислотного складу культивованих грибів до "ідеального білку". Особливу увагу приділено есенціальним (лімітуючим) амінокислотам, їх вмісту в складі нових видів ковбасних виробів

High-resolution X-ray spectroscopy of rare events: a different look at local structure and chemistry

The combination of large-acceptance high-resolution X-ray optics with bright synchrotron sources permits quantitative analysis of rare events such as X-ray fluorescence from very dilute systems, weak fluorescence transitions or X-ray Raman scattering. Transition-metal Kβ fluorescence contains information about spin and oxidation state; examples of the characterization of the Mn oxidation states in the oxygen-evolving complex of photosystem II and Mn-consuming spores from the marine bacillus SG-1 are presented. Weaker features of the Kβ spectrum resulting from valence-level and 'interatomic' ligand to metal transitions contain detailed information on the ligand-atom type, distance and orientation. Applications of this spectral region to characterize the local structure of model compounds are presented. X-ray Raman scattering (XRS) is an extremely rare event, but also represents a unique technique to obtain bulk-sensitive low-energy

Thermodynamics-Based Models of Transcriptional Regulation by Enhancers: The Roles of Synergistic Activation, Cooperative Binding and Short-Range Repression

Quantitative models of cis-regulatory activity have the potential to improve our mechanistic understanding of transcriptional regulation. However, the few models available today have been based on simplistic assumptions about the sequences being modeled, or heuristic approximations of the underlying regulatory mechanisms. We have developed a thermodynamics-based model to predict gene expression driven by any DNA sequence, as a function of transcription factor concentrations and their DNA-binding specificities. It uses statistical thermodynamics theory to model not only protein-DNA interaction, but also the effect of DNA-bound activators and repressors on gene expression. In addition, the model incorporates mechanistic features such as synergistic effect of multiple activators, short range repression, and cooperativity in transcription factor-DNA binding, allowing us to systematically evaluate the significance of these features in the context of available expression data. Using this model on segmentation-related enhancers in Drosophila, we find that transcriptional synergy due to simultaneous action of multiple activators helps explain the data beyond what can be explained by cooperative DNA-binding alone. We find clear support for the phenomenon of short-range repression, where repressors do not directly interact with the basal transcriptional machinery. We also find that the binding sites contributing to an enhancer's function may not be conserved during evolution, and a noticeable fraction of these undergo lineage-specific changes. Our implementation of the model, called GEMSTAT, is the first publicly available program for simultaneously modeling the regulatory activities of a given set of sequences

Fumarate Reductase Activity Maintains an Energized Membrane in Anaerobic Mycobacterium tuberculosis

Oxygen depletion of Mycobacterium tuberculosis engages the DosR regulon that coordinates an overall down-regulation of metabolism while up-regulating specific genes involved in respiration and central metabolism. We have developed a chemostat model of M. tuberculosis where growth rate was a function of dissolved oxygen concentration to analyze metabolic adaptation to hypoxia. A drop in dissolved oxygen concentration from 50 mmHg to 0.42 mmHg led to a 2.3 fold decrease in intracellular ATP levels with an almost 70-fold increase in the ratio of NADH/NAD+. This suggests that re-oxidation of this co-factor becomes limiting in the absence of a terminal electron acceptor. Upon oxygen limitation genes involved in the reverse TCA cycle were upregulated and this upregulation was associated with a significant accumulation of succinate in the extracellular milieu. We confirmed that this succinate was produced by a reversal of the TCA cycle towards the non-oxidative direction with net CO2 incorporation by analysis of the isotopomers of secreted succinate after feeding stable isotope (13C) labeled precursors. This showed that the resulting succinate retained both carbons lost during oxidative operation of the TCA cycle. Metabolomic analyses of all glycolytic and TCA cycle intermediates from 13C-glucose fed cells under aerobic and anaerobic conditions showed a clear reversal of isotope labeling patterns accompanying the switch from normoxic to anoxic conditions. M. tuberculosis encodes three potential succinate-producing enzymes including a canonical fumarate reductase which was highly upregulated under hypoxia. Knockout of frd, however, failed to reduce succinate accumulation and gene expression studies revealed a compensatory upregulation of two homologous enzymes. These major realignments of central metabolism are consistent with a model of oxygen-induced stasis in which an energized membrane is maintained by coupling the reductive branch of the TCA cycle to succinate secretion. This fermentative process may offer unique targets for the treatment of latent tuberculosis

Integrating Signals from the T-Cell Receptor and the Interleukin-2 Receptor

T cells orchestrate the adaptive immune response, making them targets for immunotherapy. Although immunosuppressive therapies prevent disease progression, they also leave patients susceptible to opportunistic infections. To identify novel drug targets, we established a logical model describing T-cell receptor (TCR) signaling. However, to have a model that is able to predict new therapeutic approaches, the current drug targets must be included. Therefore, as a next step we generated the interleukin-2 receptor (IL-2R) signaling network and developed a tool to merge logical models. For IL-2R signaling, we show that STAT activation is independent of both Src- and PI3-kinases, while ERK activation depends upon both kinases and additionally requires novel PKCs. In addition, our merged model correctly predicted TCR-induced STAT activation. The combined network also allows information transfer from one receptor to add detail to another, thereby predicting that LAT mediates JNK activation in IL-2R signaling. In summary, the merged model not only enables us to unravel potential cross-talk, but it also suggests new experimental designs and provides a critical step towards designing strategies to reprogram T cells