How growth affects the fate of cellular metabolites
Kooijman, S. A. L. M. and Segel L. A. 2005.
How growth affects the fate of cellular metabolites.
Bull. Math. Biol. 67: 57 - 77
Abstract
Cellular metabolites frequently have more than a single function
in the cell. For example they may be sources of energy as well as
building blocks for several macromolecules. The relative cellular
needs for these different functions depend on environmental and
intracellular factors. The intermediary products of
phosphorylation of pyruvate by mitochondria, for example, are used
for growth, while the released ATP is used for both growth and
maintenance. Since maintenance has priority over growth, and
maintenance is proportional to a cell's mass, a cell's need for
ATP versus building blocks depends on the growth rate, and hence
on substrate availability. We show how the concept of Synthesising
Units (SUs) in linear and cyclic pathways takes care of the
correct variation of the ATP/building block ratio in the context
of the Dynamic Energy Budget (DEB) theory. This can only be
achieved by an interaction between subsequent SUs in transferring
metabolites. Apart from this interaction we also needed an
essential feature of the performance of the pathway in the DEB
context: the relative amount of enzymes varies with the growth
rate in a special way. We solved an important consistency problem
between the DEB model at the whole-cell level and a model for
pathway dynamics. We observe that alternative whole-cell models,
such as the Marr-Pirt model, that keep the relative amount of
enzymes constant, and hence independent of the growth rate, will
have problems in explaining how pathways can meet cell's
growth-dependent needs for building blocks versus ATP.