“Background: Metabolism and its regulation constitute a la


“Background: Metabolism and its regulation constitute a large fraction of the molecular drug discovery activity within cells. The control of cellular metabolic state is mediated by numerous molecular mechanisms, which in effect position the metabolic network flux

state at specific locations within a mathematically-definable steady-state flux space. Post-translational regulation constitutes a large class of these mechanisms, and decades of research indicate that achieving a network flux state through post-translational metabolic regulation is both a complex and complicated regulatory problem. No analysis method for the objective, top-down assessment of such regulation problems in large biochemical networks has been presented and demonstrated.\n\nResults: We show that the use of Monte Carlo sampling of the steady-state flux space of a cell-scale metabolic system in conjunction with Principal Component Analysis and eigenvector rotation results in a low-dimensional and biochemically interpretable decomposition of the steady flux states of the system. This decomposition comes in the form of a low number of small reaction sets whose flux variability accounts for nearly all of the flux variability in the entire system. This result indicates an underlying simplicity and implies that the regulation of a relatively low number of reaction sets can essentially determine the flux state of the entire network in the given growth environment.\n\nConclusion:

We demonstrate how our top-down analysis of networks can be used to determine key regulatory requirements independent of specific parameters and

mechanisms. Our approach complements the reductionist approach to elucidation FDA-approved Drug Library clinical trial of regulatory mechanisms and facilitates the development of our understanding of global regulatory strategies in biological networks.”
“BACKGROUND: Belnacasan solubility dmso Propionic acid is widely used in chemical and allied industries and can be produced by biocultivation in a clean and environmentally friendly route. Recovery of the acid from the dilute stream from the bioreactor is an economic problem. Reactive extraction is a promising method of recovering the acid but suffers from toxicity problems of the solvent employed. There is thus a need for a non-toxic solvent or a combination of less toxic extractants in a non-toxic diluent that can recover acid efficiently.\n\nRESULTS: The effect of different extractants (tri-n-butylphosphate (TBP), tri-n-octylamine (TOA) and Aliquat 336) and their mixed binary solutions in sunflower oil diluent was studied to find the best extractant-sunflower oil combination. Equilibrium complexation constant, K(E), values of 4.02, 3.13 and 1.87 m(3) kmol(-1) were obtained for propionic acid extraction using Aliquat 336, TOA and TBP, respectively, in sunflower oil. The effect of different modifiers (1-decanol, methylisobutyl ketone, butyl acetate and dodecanol) on the extraction was also studied and it was found that modifiers enhance extraction, with 1-decanol found to be the best.

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