Why Is the Cell So Complex? - Molecular Theory of the Living Cell - page 577

The dynamic complexity of the cell refers to the complexity of the interactions
among the molecular and macromolecular components of the cell organized in space
and time (constituting various dissipatons ). In 1999, Bernard Jacq and his colleagues
coined the term “interactome” to represent the whole set of molecular interactions
in cells (see Sect. 9.3 ). There are two (and only two) kinds of interactions in the cell -
(1) covalent (e.g., the phosphoryl group transfer from ATP to a protein catalyzed by
a kinase) and (2) noncovalent interactions (e.g., hormone binding to its receptor,
electrostatic interactions among charged molecules) (Sect. 3.2 ). In general, the
interaction energies of the former are about 20 times those of the latter, that is,
50-100 kcal/mol versus 2-5 kcal/mol.
The metabolic maps or metabolism charts summarize all the biochemical reactions
occurring inside the cell, and the arrows in these charts symbolize covalent
interactions each catalyzed by at least one enzyme, supported by noncovalent
interactions such as substrate and product binding to enzymes. The complexity of
the metabolic map is evident in the large numbers of the biochemicals (represented by
nodes numbering 500-600) and the chemical reactions (represented by directed edges
or arrows). Some nodes such as acetyl Co-A has a dozen edges connected to them.
One way to estimate the complexity of the metabolic map would be to count all the
nodes and the edges in it and all the symbols needed to describe each node and edge.
Unlike the metabolic maps (or networks) whose nodes are biochemicals and the
enzymes catalyzing their transformations are hidden, the signal transduction
pathways focus on the intracellular proteins that interact either covalently (mostly
through phosphoryl transfer) or noncovalently (through electrostatic, hydrophobic,
and/or hydrogen-bonding interactions).
Since the living cell can be viewed as an organized system of the four key
molecular components - DNA (d), RNA (r), proteins (p), and biochemicals (b) (see
Fig. 10.2 ) and, since the existence of the d-d, p-p, and b-b interactomes is well
established (see Table 9.6 ), with the last interactome being identified with the tradi-
tional metabolic pathways, it seems logical to raise the question: Is there any experi-
mental evidence for the existence of the r-r (or RNA-RNA) interactome? The answer
to this question will critically depend on how the r-r interaction or correlation, both
linear and nonlinear, is defined (see Table 12.12 ) . Just as the d-d interactome is based
on defining the d-d interaction as the “digenic lethal relation,” or the relation between
two genes whose simultaneous mutations leading to a lethal phenotype of the cell
(Costanzo et al. 2010), so one way to define the r-r interaction is in terms of the
similarity of the RNA trajectories (i.e., ribons ) between two or more RNA molecules
as measured with microarrays (Sects. 12.2 and 12.8 ). One way to describe the
similarity among ribons in cells is to utilize ribonoscopy as explained in Sect.
12.8.3 . Based on the ribonic spectra such as shown in Fig. 12.12 ,itispossibleto
identify those RNAmolecules whose trajectories (i.e., ribons or RNAwaves) have the
same node numbers. Thus, 1 RNA molecule from the glycolytic pathway, 4 from the
protein folding pathway, 5 from the secretion pathway, 4 from the transcription
pathway, 5 from the protein synthesis pathway, 3 from the sterol metabolic pathway,
and about 65 from the group of 294 RNA molecules with unknown functions all have
the same node number 20, indicating that they exhibit a similar kinetic behavior or