Abstract
The kinetics of the association between cytochrome P450 (P450) and microsomal epoxide hydrolase (mEH) was studied by means of resonant mirror based on the principle of surface plasmon resonance. The dissociation equilibrium constants (KD) for the affinity of P450 enzymes for mEH were estimated by resonant mirror using an optical biosensor cell covalently bound to rat mEH. Comparable KD values were obtained for CYP1A1 and 2B1, and these were greater by one order of magnitude than that for the CYP2C11. To clarify the influences of P450 enzymes on the catalytic activity of mEH, the hydrolyzing activity for styrene oxide and benzo(a)pyrene-7,8-oxide [B(a)P-oxide] was analyzed in the presence or absence of P450s. Styrene oxide hydrolysis was activated by all P450s including the CYP1A, 2B, 2C, and 3A subfamilies. In agreement with the association affinity determined by resonant mirror, CYP2C11 tends to have enhanced activity for styrene oxide hydrolysis. On the other hand, B(a)P-oxide hydrolysis was enhanced by only CYP2C11 while CYP1A1 and CYP2B1 had no effect. These results suggest that (1) many P450 enzymes associate nonspecifically with mEH, (2) the CYP2C11 plays a greater role in the association/activation of mEH and (3) the P450-mediated activation of mEH depends upon the substrate of mEH.
| Original language | English |
|---|---|
| Pages (from-to) | 275-280 |
| Number of pages | 6 |
| Journal | Archives of Biochemistry and Biophysics |
| Volume | 402 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jun 15 2002 |
| Externally published | Yes |
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Keywords
- Benzo(a)pyrene-7,8-oxide
- Cytochrome P450
- Microsomal epoxide hydrolase
- Protein-protein interaction
- Styrene oxide
- Surface plasmon resonance
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Activation of microsomal epoxide hydrolase by interaction with cytochromes p450 : Kinetic analysis of the association and substrate-specific activation of epoxide hydrolase function. / Taura, K. I.; Yamada, H.; Naito, E.; Ariyoshi, Noritaka; Mori, M. A.; Oguri, K.
In: Archives of Biochemistry and Biophysics, Vol. 402, No. 2, 15.06.2002, p. 275-280.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Activation of microsomal epoxide hydrolase by interaction with cytochromes p450
T2 - Kinetic analysis of the association and substrate-specific activation of epoxide hydrolase function
AU - Taura, K. I.
AU - Yamada, H.
AU - Naito, E.
AU - Ariyoshi, Noritaka
AU - Mori, M. A.
AU - Oguri, K.
PY - 2002/6/15
Y1 - 2002/6/15
N2 - The kinetics of the association between cytochrome P450 (P450) and microsomal epoxide hydrolase (mEH) was studied by means of resonant mirror based on the principle of surface plasmon resonance. The dissociation equilibrium constants (KD) for the affinity of P450 enzymes for mEH were estimated by resonant mirror using an optical biosensor cell covalently bound to rat mEH. Comparable KD values were obtained for CYP1A1 and 2B1, and these were greater by one order of magnitude than that for the CYP2C11. To clarify the influences of P450 enzymes on the catalytic activity of mEH, the hydrolyzing activity for styrene oxide and benzo(a)pyrene-7,8-oxide [B(a)P-oxide] was analyzed in the presence or absence of P450s. Styrene oxide hydrolysis was activated by all P450s including the CYP1A, 2B, 2C, and 3A subfamilies. In agreement with the association affinity determined by resonant mirror, CYP2C11 tends to have enhanced activity for styrene oxide hydrolysis. On the other hand, B(a)P-oxide hydrolysis was enhanced by only CYP2C11 while CYP1A1 and CYP2B1 had no effect. These results suggest that (1) many P450 enzymes associate nonspecifically with mEH, (2) the CYP2C11 plays a greater role in the association/activation of mEH and (3) the P450-mediated activation of mEH depends upon the substrate of mEH.
AB - The kinetics of the association between cytochrome P450 (P450) and microsomal epoxide hydrolase (mEH) was studied by means of resonant mirror based on the principle of surface plasmon resonance. The dissociation equilibrium constants (KD) for the affinity of P450 enzymes for mEH were estimated by resonant mirror using an optical biosensor cell covalently bound to rat mEH. Comparable KD values were obtained for CYP1A1 and 2B1, and these were greater by one order of magnitude than that for the CYP2C11. To clarify the influences of P450 enzymes on the catalytic activity of mEH, the hydrolyzing activity for styrene oxide and benzo(a)pyrene-7,8-oxide [B(a)P-oxide] was analyzed in the presence or absence of P450s. Styrene oxide hydrolysis was activated by all P450s including the CYP1A, 2B, 2C, and 3A subfamilies. In agreement with the association affinity determined by resonant mirror, CYP2C11 tends to have enhanced activity for styrene oxide hydrolysis. On the other hand, B(a)P-oxide hydrolysis was enhanced by only CYP2C11 while CYP1A1 and CYP2B1 had no effect. These results suggest that (1) many P450 enzymes associate nonspecifically with mEH, (2) the CYP2C11 plays a greater role in the association/activation of mEH and (3) the P450-mediated activation of mEH depends upon the substrate of mEH.
KW - Benzo(a)pyrene-7,8-oxide
KW - Cytochrome P450
KW - Microsomal epoxide hydrolase
KW - Protein-protein interaction
KW - Styrene oxide
KW - Surface plasmon resonance
UR - http://www.scopus.com/inward/record.url?scp=0037098410&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037098410&partnerID=8YFLogxK
U2 - 10.1016/S0003-9861(02)00079-6
DO - 10.1016/S0003-9861(02)00079-6
M3 - Article
C2 - 12051674
AN - SCOPUS:0037098410
VL - 402
SP - 275
EP - 280
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
IS - 2
ER -