Biology Reference
In-Depth Information
the tendency of organisms to resist death. A major additional form of organi-
zation involves cycles. Cycles appear in biological accounts at various levels
of organization (many of the best known involve relations between organisms
and their environment, such as the nitrogen cycle), but I will focus on cycles
at the level of basic metabolic processes. The pioneers in biochemistry at the
turn of the twentieth century generally assumed that the chemical reactions in
living organisms occurred serially and hence the pathways of reactions would be
linear. They sought to identify the intermediates in, for example, the oxidation
of fatty acids or the oxidation of glucose to alcohol that could be generated
through known chemical reactions (oxidations or reductions of substrates, addi-
tions or removals of carboxyl groups, etc.). Often, however, they could go
only so far in arranging intermediates in linear sequences; proposed reaction
sequences would yield a substance which could not be processed in the same
manner. The discovery of perhaps the most famous biochemical cycle, the citric
acid cycle, resulted from such a circumstance. After adopting Wieland's (1913)
account of oxidation as involving the removal of a pair of hydrogen atoms from
a substrate (dehydrogenation), Thorsten Thunberg established that a number of
organic acids (lactic acid, succinic acid, fumaric acid, malic acid, citric acid, etc.)
could all be oxidized in cellular extracts in such a manner (Thunberg, 1920). He
then tried to fit the reactions together in a coherent pathway involving a chain of
reactions.
14
Relatively easily he was able to fit the various compounds together
into the sequence:
Succinic acid
→
fumaric acid
→
malic acid
→
oxaloacetic acid
→
pyruvic acid
→
acetic acid
He then faced a problem in specifying what happened next - it was not possible
to remove two hydrogen atoms from acetic acid. In response to this problem,
Thunberg offered a bold proposal - he proposed 'a reaction in which two acetate
molecules are simultaneously each deprived of one hydrogen atom, with the
joining of their carbon chains into one. The substance which must therefore form
is succinic acid' (Thunberg, 1920, passage translated by Holmes, 1986, p. 69).
The reaction Thunberg proposed was the following:
2CH
3
-COOH
→
COOH-CH
2
-CH
2
-COOH
+
H
2
This resulted in the pathway becoming a cycle, as shown in Figure 3a.
14
Thunberg actually had the idea of a sequence of reactions as early as 1913, before he encountered Wieland's
conception of dehydrogenation: 'The oxidative processes in living cells must be thought of as forming chain
reactions, a series of reactions connected to one another in such a way that, by and large, none of the links
in the reaction chain can proceed more rapidly than the others' (Thunberg, 1913, translated in Holmes, 1986,
p. 68)
