Biology Reference
In-Depth Information
are active in living cells and determine their structure by X-ray crystallography.
For membrane proteins, this is still a challenge, but progress is being made.
The mechanism of quite a few enzymes is now considered to be understood
reasonably well (although fundamental issues remain (Scrutton et al., 1999;
Sutcliffe & Scrutton, 2000)) and so are regulatory mechanisms in the sense of
which molecule might bind to which other molecule and regulate the activity
of the latter. Pathways and networks of metabolism, gene expression and signal
transduction have been mapped.
1.4. Cell Biology: The living cell
Near the end of the twentieth century genomics revolutionized this landscape.
This revolution was preceded by a long and ever accelerating progress in bio-
chemistry, molecular biology and the related disciplines of microbiology and
biophysics and led to a combined discipline: cell biology. It defined the orga-
nization of life at the cellular level in qualitative terms of its molecules. With
apologies for the readers who know their cell biology, but with due respect to
the philosophers who may not quite do so but are interested in systems biology,
we shall now describe the essence of this definition.
Early on, biochemistry had shown that all (most) chemical conversions carried
out by living organisms occurred in a number of simpler steps such as dehydra-
tion, transfer of phosphate from ATP, dehydrogenation and isomerization. Each
of these is catalysed by a protein, called an enzyme, which consists of one or
a few chains of amino acids and sometimes an additional organic or inorganic
chemical molecule or ion, folded into a complex structure. The amino acids are
virtually limited to a set of 20 types. The protein is different for every type
of molecule that needs to be converted. This led to the concept of metabolism
consisting of large networks of chemical reactions through which mass flows,
with a correspondence of every step to a protein (Beadle & Tatum, 1941). The
metabolic networks are extremely powerful chemically, being able to convert
many types of molecule into many other types, and many thousands of metabo-
lites are known (Kell, 2004). The former correspond to almost anything that
occurs in the environment of living organisms and is useful to them as food.
The latter are suitable building blocks for the organism. The pluripotency of
metabolism appears limited only by impossibilities stemming from a number of
fundamental laws, such as the impossibility to create chemical elements from
other chemical elements and the impossibility to generate Gibbs' free energy
(Westerhoff & van Dam, 1987). The consequence is that there are metabolic
networks ensuring that sufficient of each of these commodities is harvested
from the food and supplied to biosynthesis. Metabolism is a network that makes
biomass from food, although it does not seem to have evolved to be efficient in
the thermodynamic sense (Kell et al., 2005; Westerhoff et al., 1983).
