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Liver      319


                 A. Cytochrome P450-dependent monooxygenases: reactions

                                                                                                   R
                   Apolar substrate
                                                                                                  CH 2
                     H                                                                          O
                                                                   H 3 C
                OO              F  A      N  A
                                                              O
                                                         O
                                              P
                2H                                          R
                         1
                      Fe                                                                             R
                                                      H           H
                                                         O        O                                  C
                 H O            F  A      N  A                       CH 2                      HO  H    O
                  2
                                              P
                 (H   ) O
                                                             O
                                                         O                     O
                 Oxygenated product                         R

                   1 Monooxygenase              a) Hydroxylation  b) Hydroxylation  c) Epoxidation  d) Dealkylation
                     1.14.n.n [heme P450]         aromatic       alipathic


                 B. Reaction mechanism


                                   HO                                         H
                            Product                                                      Substrate
                                                     S   Fe 3

                                            6                                 1



                                                          Resting
                  S   Fe 3                                state                         S   Fe 3
                           H
                           O                                                                     H



                                                          F   A
                                      N   A
                                            P                                                        O 2
                                                                                   e
                           5
                                                                                              2
                                      N   A
                                                          F   A
                                            P


                                     “Activated                                                     O
                  S   Fe 4  O        oxygen”                                  e         S   Fe 2  O
                                                          Cyt P450
                           H                              reductase                              H


                                            4                                3
                                                                 OH
                                                     S   Fe 3  O
                                  H O                                                 H
                                    2
                                                              H
                                             H




           Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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