Biology Reference
In-Depth Information
Thunberg's proposed cycle was speculative, and a good deal of research
went into trying to determine the actual intermediates in the oxidation of three
carbon sugars until Krebs and William Johnson (1937) published their account
of the citric acid cycle (also known as the tricarboxylic acid cycle and later as
the Krebs cycle). As shown in Fig. 3, instead of two molecules of acetic acid
combining to form succinic acid, Krebs proposed that oxaloacetic acid combined
with a three-carbon substance, which Krebs designated simply as
triose
,to
generate citric acid. He then proposed that citric acid underwent a sequence of
reactions resulting in succinic acid. After the discovery of coenzyme A in the
1940s, biochemists recognized that it was acetyl-CoA that entered the cycle by
combining with oxaloacetic acid to form citric acid.
What is noteworthy about Thunberg's and Krebs' research, as well as that
of many other biochemists who proposed cycles in the early decades of the
twentieth century, is that they were guided purely by the desire to articulate
plausible pathways of chemical reactions that would provide complete accounts
from known starting points to appropriate endpoints. Cyclic organization was
not construed as theoretically significant. Subsequently, as the ubiquity of cycles
became apparent, some theorists did take up the question of why cycles were so
common. One advantage of cyclically organized processes is that they provide a
means of effective negative feedback regulation - only when the products of the
cycle are generated will new substances be able to enter the cycle. But they play
an even more significant role in organizing chemical operations in biological
systems.
An illuminating perspective on the function of cycles in biochemistry is
offered by Tibor Gánti (see his 2003 for a synthetic statement of an account
which he initially advanced in the 1970s). Gánti's project has been to identify the
simplest chemical system that exhibits the distinctive features of life, a system
he calls the
chemoton
.
15
In pursuing this project, Gánti takes his lead from the
minimal biological system exhibiting the properties of life, the cell. He identifies
three subsystems as common to all cells: 'the cytoplasm, the membrane, and
the genetic substance'. His analysis plays particular attention to the cytoplasm,
which he characterizes as 'the chemical motor'.
16
He then notes a general feature
15
It is important to note that Gánti is not trying to provide a detailed account of first organisms or the
origins of life but, as Griesemer & Szathmáry (forthcoming) emphasize, a heuristic model to help probe the
organization required in living systems: 'the chemoton model is not intended as an accurate representation
which, if implemented exactly, could live. It is instead a heuristic guide to the organizational properties of
chemical systems that would minimally fulfill the living state'. Although the account is not presented as
accurate in detail, in another sense Gánti is seeking to be true to the systems modeled - the general architecture
of the model is intended to correspond to the architecture of the actual system. This is a feature of many
similar modeling efforts that attempt to demonstrate how, possibly, a given phenomenon might be produced.
16
Although emphasizing all three sub-systems, Gánti explicitly comments on how cytoplasm is the most
complicated and in many respects the most critical:
