Cell Language Theory, The: Connecting Mind And Matter

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“6x9” b2861 The Cell Language Theory: Connecting Mind and Matter

ligand, E and E′ refer to the two conformational states of the enzyme mol-

ecule in the “unbound” and “binding” conformations, respectively. The

concept of conformation, in contrast to that of configuration, plays a funda-

mental role in my theory of molecular biology [19, p. 25]. Conformations

are three-dimensional structures of a molecule that can be altered without

breaking or forming any covalent bonds. When such bonds need to be bro-

ken or formed during structural or shape changes, we then deal with “con-

figurations” and not “conformations” (Table 3.16). There are two distinct

mechanistic possibilities for ligand binding processes:

Induced-fit Hypothesis (IFH): L + E ↔ L•E ↔ L•E′, (3.10)

Pre-fit Hypothesis (PFH): L + E ↔ L + E′ ↔ L•E′. (3.11)

The following differences exist between these two mechanisms:

(1) IFH predicts that E cannot assume E′ without binding L. In contrast,

PFH predicts that E can assume E′ in the absence of L, the probabil-

ity P(E′) of observing E′ being dependent only on the Gibbs free

energy difference, ∆G, between E and E′, i.e., ∆G = G(E′) – G(E),

obeying the Boltzmann distribution law [169]:

P(E′) = P(E)e–∆G/RT,^ (3.12)

where R is the universal gas constant and T the absolute

temperature.

(2) The conformational change of E to E′ follows ligand binding accord-

ing to IFH, whereas it precedes ligand binding according to PFH.

(3) The energy required for the conformational transition from E to E′ is

provided by the substrate binding energy in IFH, whereas, in PFH, it

is “borrowed” temporarily from a thermal environment to be “paid

back” subsequently from the free energy of binding of L to E′ rapidly

enough to avoid violating the Second Law of Thermodynamics [14].

This mechanism is consistent with the theory of enzymic catalysis

proposed by Jencks [170] based on the Circe effect in which a part of

the free energy of substrate binding is stored in the enzyme–substrate

complex as conformational deformations of the enzyme to be utilized

later to lower the activation of free energy barrier for catalysis.

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