<P> The electrostatic states of substrate and active site must be complementary to each other . A polarized negatively charged amino acid side chain will repel uncharged substrate . But if the transition state involves the formation of a ion centre then the side chain will now produce a favourable interaction . </P> <P> Many enzymes including serine protease, cysteine protease, protein kinase and phosphatase evolved to form transient covalent bonds between them and their substrates to lower the activation energy and allow the reaction to occur. This process can be divided into 2 steps: formation and breakdown. The former step is rate - limit step while the later step is needed to regenerate intact enzyme . </P> <P> Nucleophilic catalysis: This process involves the donation of electrons from the enzyme's nucleophile to a substrate to form a covalent bond between them during the transition state . The strength of this interaction depends on two aspects.: the ability of the nucleophilic group to donate electrons and the electrophile to accept them . The former one is mainly affected by the basicity (the ability to donate electron pairs) of the species while the later one is in regard to its pK . Both groups are also affected by their chemical properties such as polarizability, electronegativity and ionization potential . Amino acids that can form nucleophile including serine, cysteine, aspartate and glutamine . </P> <P> Electrophilic catalysis: The mechanism behind this process is exactly same as nucleophilic catalysis except that now amino acids in active site act as electrophile while substrates are nucleophiles . This reaction usually requires cofactors as the amino acid side chains are not strong enough in attracting electrons . </P>

Substrates contain an active site to which the enzyme attaches