Substrate utilization in mammalian cells

Substrate Utilization in Mammalian Cells Lactate as Substrate... 

However, various assays utilizing nonstandardized sources of HDAC protein preparations and substrates appear to generate large variations in the resulting data. As an example. Table 6.1 summarizes the observed variations in the recently reported in vitro data for the effects of SAHA on individual H DAC isoforms [14,19-23]. HDAC isoforms used for in vitro screening assays have been expressed in Escherichia coli (HDACl, 3), Picchia, SF9 insect cells (HDACl-11) or mammalian cells (recombinant HDACl, 3) these sources may lead to differential enzyme activities. 

Some of the efforts, so far, to model such membrane bioreactors seem to not have considered the complications that may result from the presence of the biomass. Tharakan and Chau [5.101], for example, developed a model and carried out numerical simulations to describe a radial flow, hollow fiber membrane bioreactor, in which the biocatalyst consisted of a mammalian cell culture placed in the annular volume between the reactor cell and the hollow fibers. Their model utilizes the appropriate non-linear kinetics to describe the substrate consumption however, the flow patterns assumed for the model were based on those obtained with an empty reactor, and would probably be inappropriate, when the annular volume is substantially filled with microorganisms. A model to describe a hollow-fiber perfusion system utilizing mouse adrenal tumor cells as biocatalysts was developed by Cima et al [5.102]. In contrast, to the model of Tharakan and Chau [5.101], this model took into account the effect of the biomass, and the flow pattern distribution in the annular volume. These effects are of key importance for conditions encountered in long-term cell cultures, when the cell mass is very dense and small voids can completely distort the flow patterns. However, the model calculations of Cima et al. [5.102] did not take into account the dynamic evolution of the cell culture due to growth, and its influence on the permeate flow rate. Their model is appropriate for constant biocatalyst concentration. 

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