Catalytic Selectivity of CYP

Analysis of the literature indicates that three major forms of CYPs are involved in the metabolism of pharmaceuticals in man CYP2D6, CYP2C9 and CYP3A4, CYP1A2, CYP2C19 and CYP2E1 are also involved, but this involvement is much less extensive. The catalytic selectivity of the major CYPs has been reviewed [1]. 

All the template models produced have the same common features of a basic nitrogen atom at a distance of 5-7 A from the site of metabolism which is in general on or near a planar aromatic system. It is currently believed that aspartic acid residue 301 provides the carboxylate residues which binds the basic nitrogen of the substrates. 

Beside the actual steric bulk of the substituent, cyclopropyl is much more stable to hydrogen abstraction than other alkyl functions and represents an ideal terminal group. These changes make betaxolol a compound with much improved pharmacokinetics compared to its lipophilic analogues. 

The mean dimensions ( SD) for the eight compounds (a = 6.7 0.8 A, C = 133 20°) illustrates the degree of overlap achieved. Like CYP2D6 the catalytic selectivity of CYP2C9 is dominated by substrate-protein interactions. 

The mechanism of action of CYPs is radical rather than electrophilic and the actual substitution pattern is important the role of chlorine is one of blocking rather than deactivation. Many non-steroidal anti-inflammatory drugs are substrates for the 

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