Premium
Functional Interactions Between CYP1A2 and CYP2B4 Require Both Enzymes to Reside in the Same Phospholipid Vesicle
Author(s) -
Reed James Robert,
Backes Wayne L.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.749.3
Subject(s) - vesicle , enzyme , chemistry , cyp1a2 , biochemistry , phospholipid , metabolism , ternary complex , reductase , cytochrome p450 , membrane
The goal of this study was to determine if the interactions between different P450 enzymes (CYP1A2 and CYP2B4) required both enzymes to be present in the same lipid vesicles, or if the proteins could interact when in different vesicles. When a single P450 and P450 reductase (CPR) were incorporated into separate vesicles, extremely slow reduction rates were observed, suggesting that the enzymes were anchored in the vesicles. Next, metabolism by systems were compared when two P450s (and the requisite CPR) were incorporated into separate vesicles (separate vesicle systems) and when both P450s and CPR were incorporated in the same vesicles (ternary system). In the ternary system, metabolism by CYP2B4 was significantly inhibited and that by CYP1A2 was stimulated by the presence of the alternate P450. In contrast, in the separate vesicles, the P450s were unable to interact and simple additive metabolism was observed. These results clearly demonstrate that the observed alterations in P450 metabolism require both P450s to be present in the same vesicles, and support a mechanism whereby these P450s form a physical complex in the membrane environment. (Supported by NIEHS R01‐004344).