Metabolic modeling cellular metabolism

Due to its central role in toxicant metabolism, the liver is one of the first organs being constructed in the Virtual Tissue Research Project. Physiologically based pharmacokinetic modeling, cellular systems, and molecular networks are integrated to mimic the multitude of activities performed by the liver. Once completed, this innovative project will be an invaluable resource for accessible, accurate, and responsible prediction of liver toxicity. 

Analytical models of the heart are a reality. They are based on detailed descriptions of cardiac tissue architecture and anatomy, including the coronary vasculature. In sihco cardiac tissues possess realistic passive mechanical properties, and both electrical and mechanical activity can be simulated with high accuracy. Descriptions of key components of cellular metabolism have been introduced, as have models of drug-receptor interactions. 

Subsequent studies have confirmed that the reason for this discrepancy is that the rat is able to rapidly metabolise P-carotene to retinol in the intestine, through the action of intestinal dioxygenase. In contrast humans absorb P-carotene systemically such that plasma levels of P-carotene increase to levels not found in the rodent. A more appropriate animal model is the ferret, which shows a similar metabolism to humans. High levels of plasma P-carotene in the ferret induce the cellular transcription factors c-fos and c-jun, and squamous metaplasia is seen in the lung with or without exposure to cigarette smoke (SCF, 2000). Even after the investment of all these resources it has not been possible for the EU Scientific Committee on Food to set an ADI. 

In 1976, Hamish Munro proposed a model for the translational control of ferritin synthesis (Zahringer et al., 1976), which not only represents a crucial and remarkably far-sighted contribution to our understanding of cellular iron metabolism, but also in the more general context of the posttranscriptional control of gene expression. 

Consequently, we have to touch upon at least some operational issues to define our approach to the ways and means of constructing models of metabolism. At the most basic level, surveying the current literature, we face a strong dichotomy between a quest for elaborate large-scale models of cellular pathways and minimal (skeleton) models, tailored to explain specific dynamic phenomena only. 

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