A physical model of cell metabolism

Cell metabolism is characterized by three fundamental energy demands: to sustain cell maintenance, to trigger aerobic fermentation and to achieve maximum metabolic rate. The transition to aerobic fermentation and the maximum metabolic rate are currently understood based on enzymatic cost constraints. Yet, we are lacking a theory explaining the maintenance energy demand. Here we report a physical model of cell metabolism that explains the origin of these three energy scales. Our key hypothesis is that the maintenance energy demand is rooted on the energy expended by molecular motors to fluidize the cytoplasm and counteract molecular crowding. Using this model and independent parameter estimates we make predictions for the three energy scales that are in quantitative agreement with experimental values. The model also recapitulates the dependencies of cell growth with extracellular osmolarity and temperature. This theory brings together biophysics and cell biology in a tractable model that can be applied to understand key principles of cell metabolism

Limits of aerobic metabolism in cancer cells

Cancer cells exhibit high rates of glycolysis and glutaminolysis. Glycolysis can provide energy and glutaminolysis can provide carbon for anaplerosis and reductive carboxylation to citrate. However, all these metabolic requirements could be in principle satisfied from glucose. Here we investigate why cancer cells do not satisfy their metabolic demands using aerobic biosynthesis from glucose. Based on the typical composition of a mammalian cell we quantify the energy demand and the OxPhos burden of cell biosynthesis from glucose. Our calculation demonstrates that aerobic growth from glucose is feasible up to a minimum doubling time that is proportional to the OxPhos burden and inversely proportional to the mitochondria OxPhos capacity. To grow faster cancer cells must activate aerobic glycolysis for energy generation and uncouple NADH generation from biosynthesis. To uncouple biosynthesis from NADH generation cancer cells can synthesize lipids from carbon sources that do not produce NADH in their catabolism, including acetate and the amino acids glutamate, glutamine, phenylalanine and tyrosine. Finally, we show that cancer cell lines have an OxPhos capacity that is insufficient to support aerobic biosynthesis from glucose. We conclude that selection for high rate of biosynthesis implies a selection for aerobic glycolysis and uncoupling biosynthesis from NADH generation

The Territorial Inequalities In The Location Of The Foreign Direct Investment In The 90s: The Spanish Case

One of the main characteristics on the world economy during the second half of the eighties was the boom registered by the international investment, in particular, going to the Spanish economy. But the nineties were also characterised by the consolidation of these Foreign Direct Investment (FDI) inflows. In addition, the UNCTAD, in their World Investment Report (WIR) 2001, alert about a pattern of concentration of this FDI in the more developed countries in the last years that it is pushing to a concentration within a national environment in the more developed regions too. So, inside this context of concentration of the FDI in the international environment, and considering that the Spanish economy was one of the most important destinations for the FDI, the present paper wants to analyse if this same behaviour pattern of FDI is verified within the Spanish economy. The data will show that the geographical concentration of the FDI in the more developed regions exists and that is increasing along the time. A new strategy based on the relocation of foreign capital is generated from the international economic crisis. But the Spanish economy and, very in particular, the Madrids community, they have never stopped to be attractive for the foreign investor. Even, the concentration of the foreign capital in this region is intensified along the time, harming the less developed regions of the Spanish economy. So, this paper wants to get the attention on this high degree of concentration of this foreign capital in the Spanish economy in terms of other macroeconomic variables, as the GDP or the GFCF. As result, a very important presence of foreign capital in the more developed areas is verified. And wide differences with regard to the remaining regions are shown