Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 471, Issue 1, Pages 20-31Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2007.11.020
Keywords
cytochrome p450 3A4; cytochrome P450BM-3 flavin domain (BMR); electron transfer kinetics; heterogeneity; spin equilibrium; allostery; testosterone; 1-pyrenebutanol; bromocriptine; alpha-naphthoflavone
Categories
Funding
- NIEHS NIH HHS [P30 ES006676, P30 ES006676-12, ES06676] Funding Source: Medline
- NIGMS NIH HHS [GM54995, R37 GM054995-12, R37 GM054995, R01 GM054995] Funding Source: Medline
Ask authors/readers for more resources
We used a rapid scanning stop-flow technique to study the kinetics of reduction of cytochrome P450 3A4 (CYP3A4) by the flavin domain of cytochrome P450-BM3 (BMR), which was shown to form a stoichiometric complex (K-D = 0.48 mu M) with CYP3A4. In the absence of substrates only about 50% of CYP3A4 was able to accept electrons from BMR. Whereas the high-spin fraction was completely reducible, the reducibility of the low-spin fraction did not exceed 42%. Among four substrates tested (testosterone, 1-pyrenebutanol, bromocriptine, or alpha-naphthoflavone (ANF)) only ANF is capable of increasing the reducibility of the low-spin fraction to 75%. Our results demonstrate that the pool of CYP3A4 is heterogeneous, and not all P450 is competent for electron transfer in the complex with reductase. The increase in the reducibility of the enzyme in the presence of ANF may represent an important element of the mechanism of action of this activator. (c) 2007 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available