Most Important Theories of Enzyme Activity

Chronology of the Most Important Theories of Enzyme Activity 

Just one year after Ostwald s hypothesis about the existence of catalysts in 1893, when nobody yet had a clear idea of the structure and composition of enzymes, Emil Fischer voiced the idea for the first time that a substrate molecule fits into the pocket of an enzyme, the lock-and-key hypothesis (Fischer, 1894). Both the lock (enzyme) as well as the key (substrate) were regarded as rigid. 

This hypothesis was modified later in many ways. According to Haldane (1965), catalysis of a reaction occurs only if a catalyst in the active center is complementary to the transition state of the substrate during the reaction. Therefore, the transition state between substrate and products fits best into a pocket close to the enzyme. The substrate molecule is subject to strain upon binding to the active center and changes its conformation to fit into the active center the key (the substrate) does not fit completely into the lock but is strained and bent. 

In a further modification of this concept, a reaction is accelerated if a catalyst stabilizes the transition state in contrast, stabilization of the ground state leads to a deceleration of the reaction. This concept of transition-state stabilization, formulated first by Haldane, was expanded later by Linus Pauling (Pauling 1946, 1948). The notion of lowering of AG 7 attributed to the stabilization of the transition state by the catalyst or to the destabilization of the ground state in comparison to the transition state is generally accepted nowadays. 

Instead of assuming a solid enzyme, in which active center the substrate molecule is bent (the concept of substrate strain), the idea was developed (Koshland 1958,1966) that enzymes can embrace the substrate molecule flexibly in the active center and effect reaction by the formation of specific interactions, the so-called induced jit . This picture is especially appropriate with allosterically activated enzymes or in situations in which part of the enzyme molecule has to turn or move over longer distances to effect catalysis (hinge movement), as for instance with most NAD(P)(H)-dependent enzymes (Stillman, 1999). 

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