Project description:Amino acids conjugated with even number carbon fatty acids using a coupling of the chloride fatty acids onto amine end of amino acids
Project description:Capuani2015 - Human Core Catabolic
Network
This model is described in the article:
Quantitative
constraint-based computational model of tumor-to-stroma
coupling via lactate shuttle
Fabrizio Capuani, Daniele De
Martino, Enzo Marinari & Andrea De Martino
Scientific Reports
Abstract:
Cancer cells utilize large amounts of ATP to sustain growth,
relying primarily on non-oxidative, fermentative pathways for
its production. In many types of cancers this leads, even in
the presence of oxygen, to the secretion of carbon equivalents
(usually in the form of lactate) in the cell’s
surroundings, a feature known as the Warburg effect. While the
molecular basis of this phenomenon are still to be elucidated,
it is clear that the spilling of energy resources contributes
to creating a peculiar microenvironment for tumors, possibly
characterized by a degree of toxicity. This suggests that
mechanisms for recycling the fermentation products (e.g. a
lactate shuttle) may be active, effectively inducing a mutually
beneficial metabolic coupling between aberrant and non-aberrant
cells. Here we analyze this scenario through a large-scale in
silico metabolic model of interacting human cells. By going
beyond the cell-autonomous description, we show that elementary
physico-chemical constraints indeed favor the establishment of
such a coupling under very broad conditions. The
characterization we obtained by tuning the aberrant
cell’s demand for ATP, amino-acids and fatty acids and/or
the imbalance in nutrient partitioning provides quantitative
support to the idea that synergistic multi-cell effects play a
central role in cancer sustainment.
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Project description:Normalized relative abundance measurement of amine-conjugated deoxycholic acids in B. fragilis P207 cultures in triplicate. All using positive ionization.
Project description:Nutrient limitation in the microenvironment of poorly perfused tumors constrains the metabolism of cancer cells. Identifying these microenvironmental constraints can provide new insight into the nutritional biochemistry of tumors and reveal metabolic liabilities of cancer cells. We have found that limitation of arginine in pancreatic cancers inhibits fatty acid synthesis by suppressing the lipogenic transcription factor SREBP1. SREBP1-driven fatty acid synthesis produces saturated and monounsaturated fatty acids. Producing these fatty acids enables cells to maintain a balance of differently saturated fatty acids needed for lipid homeostasis, even upon exposure to environments enriched in one specific class of fatty acids. Given the constraints on lipid synthesis in the microenvironment, we asked if pancreatic cancers are sensitive to exposure to fats with imbalanced levels of saturated and unsaturated fats. We found microenvironmental constraints on lipid synthesis sensitize pancreatic cancer cells and tumors to exposure to fat sources that are enriched in polyunsaturated fatty acids. Thus, amino acid restriction in the tumor microenvironment constrains lipid metabolism in pancreatic cancer, which renders pancreatic tumors incapable of maintaining lipid homeostasis upon exposure to polyunsaturated-enriched fats.
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Project description:We investigated the effects of one carbon metabolites supplementation on early embryonic development. To this end, the Bovine Embryonic Tracheal Fibroblast cell lines (EBTr; NBL-4; ATCC CCL-44) were cultured under different levels of glucose and OCM (folic acid, choline chloride, vitamin B12, and L-methionine).
Project description:Antimicrobial chemicals are widely applied to clean and disinfect food-contacting surfaces. However, the cellular response of bacteria, such as Bacillus cereus, to various disinfectants is unclear. In this study, the physiological and genome-wide transcriptional responses of B. cereus ATCC 14579 exposed to four different disinfectants (i.e., benzalkonium chloride, sodium hypochlorite, hydrogen peroxide, and peracetic acid) were analyzed. The physiological response of B. cereus to different concentrations of the disinfectants used was investigated. For each disinfectant, concentrations leading to the attenuation of growth, growth arrest, and cell death were studied in more detail. The simultaneous analysis of the transcriptional responses of B. cereus upon exposure to the different concentrations of disinfectants revealed common responses induced by the four disinfectants. Notably, genes involved in the general and oxidative stress responses were commonly up-regulated. Furthermore, the obtained results indicate that all the disinfectants also induce specific responses. Exposure to benzalkonium chloride, a disinfectant known to induce membrane damage, specifically induced genes involved in the fatty acid metabolism. Benzalkonium chloride induced-membrane damage was confirmed by fluorescence microscopy and fatty acid analysis confirmed that fatty acid composition of cell membrane was affected upon exposure to benzalkonium chloride. Sodium hypochlorite induced genes involved in sulfur and sulfur-containing amino acids metabolism, which correlated with the observed sodium hypochlorite-specific induction of oxidation of sulphydryl groups. Hydrogen peroxide and peracetic acid exposures induced genes involved in DNA damage and the SOS response. Notably, hydrogen peroxide and peracetic acid-treated cells exhibited higher mutation rates corroborating with the induced SOS response. Understanding the mechanisms displayed by microorganisms coping with disinfectants-induced stress may allow for design of more efficient sequential and/or disinfectant combination treatments in food processing environments.