Catalytic power and specificity of enzymes:

Enzymes are highly effective catalysts, commonly enhancing reaction rates by a factor of 10^5 to 10^17.

What is the energy source for the dramatic lowering of the A.E for specific reactions?

• The rearrangement of the covalent bonds during an enzyme- catalyzed reaction. Chemical reactions of many types take place between substrates and enzymes' functional groups (specific amino acid side chains, metal ions and coenzymes). Catalytic functional groups of an enzyme may form a transient covalent bond with a substrate and activate it for reaction, or a group may be transiently transferred from the substrate to the enzyme. In many cases, these reactions occur only in the enzyme active site. Covalent interaction between enzymes and substrates lower the A.E by providing an alternative, low energy reaction path.
• The non-covalent interactions between enzyme and substrate, formation of each weak interactions in the ES complex is accompanied by release of a small amount of free energy that stabilizes the interaction. The energy derived from enzyme- substrate interaction is called binding energy. Binding energy is a major source of free energy used by enzymes to lower the A.E of reactions. The interaction between substrate and enzyme in ES complex is mediated by the factors including hydrogen bonds and hydrophobic and ionic interactions, weak and non-covalent interactions.

Two fundamental and interrelated principles provide a general explanation for how enzymes use non-covalent binding energy.

• Much of the catalytic power of enzyme is ultimately derived from the free energy released in forming many weak bonds and interactions between an enzyme and its substrate. This B.E contributes to specificity as well as to catalysis.
• Weak interactions are optimized in the reaction transition state; enzyme active sites are complementary not to the substrates per but to the transition states through which substrates pass as they are converted to products during an enzymatic reaction.

Weak interactions between enzyme and substrate are optimized in the transition state:

How does an enzyme use binding energy to lower the A.E of a reaction?                                  Emil Fischer, in 1894, carried out the studies on enzyme specificity and proposed the lock and key method. 

• In case (a), Before the stick is broken, it must first be bent (transition state). In both example, magnetic interaction takes the place of weak bonding interaction between enzyme and substrate. 
• In case (b), a stickase with a magnet-lined pocket complementary in structure to the stick (substrate). Bending is impeded by the magnetic attraction between stick and atickase.
• In case (c), An enzyme with a pocket complementary to the reaction transition state helps to destabilize the stick, contributing to catalysis of the reaction. The B.E of the magnetic interaction compensates for the increase in free energy required to bend the stick.

The bound substrate must still undergo the increase in free energy needed to reach the transition state. Interaction between the stickase and non-reaching parts of the stick provide some of the energy needed to catalyze stick breakage. This "energy payment" translates into a lower net A.E and a faster reaction rate.

Real enzyme work on an analogous principle.

Some weak interaction formed in the ES complex, but the full complement of such interaction between S and E is formed only when the S reaches the transition state. The free energy (B.E) released by the formation of these interaction partially offsets the energy required to reach the top of the energy hill. The summation of the unfavorable (+ve) A.E delta G++ and the favorable (-ve) B.E delta G^B results in  a lower net activation energy.

The important principle is that weak binding interaction between the E and S provide a substantial driving force for enzymatic catalysis. The groups on the S that are involved in these weak interaction can be at some distance from the bonds that are broken or changed. The weak interaction formed only in the transition state are those that make the primary contribution to catalysis.

Why enzymes or coenzymes are so large?

Because of the requirement for multiple weak interaction to drive catalysis. An enzyme must provide functional groups for ionic, hydrogen-bond and other interaction, and must also precisely position these groups so that B.E is optimized in the transition state. Adequate binding is accompanied most readily by positioning a substrate in a cavity (active site) where it is effectively removed from water.