Category
Applied
Description
The cytochrome P450 family is composed of several metabolic enzymes found in the liver that are responsible for the processing and excretion of many xenobiotics and toxins. Cytochrome P450 2A6 (CYP2A6) is of pharmacological interest because of its key role in nicotine metabolism. Because of this, it is considered a primary target for inhibition as a potential strategy for smoking cessation and curtailing cigarette addiction. However, such a pharmacological agent is still being developed as the enzyme kinetics of CYP2A6 are not fully understood. It is also the only cytochrome that converts coumarin, a substance found in many plants, to 7-hydroxycoumarin. In this study, we probed the activity of CYP2A6 using fluorophenols, chemical substances used in many industrial applications and sometimes found as an environmental contaminant. Microsomes were mixed with coumarin in the presence of absence of several potential fluorophenols, and the results analyzed using high performance liquid chromatography (HPLC). We found that all fluorophenols were inhibitory, but di-,tri-, and tetraflurophenols were particularly effective at reducing enzyme activity.
The Inhibitory Effects of Fluorophenol on Cytochrome P450 2A6
Applied
The cytochrome P450 family is composed of several metabolic enzymes found in the liver that are responsible for the processing and excretion of many xenobiotics and toxins. Cytochrome P450 2A6 (CYP2A6) is of pharmacological interest because of its key role in nicotine metabolism. Because of this, it is considered a primary target for inhibition as a potential strategy for smoking cessation and curtailing cigarette addiction. However, such a pharmacological agent is still being developed as the enzyme kinetics of CYP2A6 are not fully understood. It is also the only cytochrome that converts coumarin, a substance found in many plants, to 7-hydroxycoumarin. In this study, we probed the activity of CYP2A6 using fluorophenols, chemical substances used in many industrial applications and sometimes found as an environmental contaminant. Microsomes were mixed with coumarin in the presence of absence of several potential fluorophenols, and the results analyzed using high performance liquid chromatography (HPLC). We found that all fluorophenols were inhibitory, but di-,tri-, and tetraflurophenols were particularly effective at reducing enzyme activity.
