Disease relevance of CYP2F1

• To better understand the mechanism for the unique toxicity profiles for both compounds, a CYP2F ortholog (CYP2F4) was isolated from rat lung and expressed using a baculovirus system [1].
• Styrene respiratory tract toxicity and mouse lung tumors are mediated by CYP2F-generated metabolites [2].

High impact information on CYP2F1

• CYP2F1 and CYP4B1, two enzymes that are expressed in lung, display only modest 3- and 2-fold respective increased abilities to metabolically activate 4-ipomeanol [3].
• The CYP2F1 gene encodes a cytochrome P450 enzyme capable of bioactivating a number of pulmonary-selective toxicants [4].
• Transient transfection studies with luciferase reporter constructs demonstrated a significant functional lung cell-specific CYP2F1 promoter region (from position -129 to +115) [4].
• These studies identified a novel LSF and its consensus sequence that may control tissue-specific expression of CYP2F1 [4].
• Several sequences homologous to known cis-elements were identified in the 5'-upstream region of the CYP2F1 promoter [4].

Biological context of CYP2F1

• CYP2F1, which encodes a P450 enzyme capable of metabolizing several mono-oxygenase substrates with the highest activity toward ethoxycoumarin, has been mapped to human chromosome 19 by somatic cell hybrid studies [5].
• CYP2F1 and CYP2F3 exclusively catalyze the dehydrogenation of 3 MI to 3-methyleneindolenine, without detectable formation of the hydroxylation or epoxidation products [6].
• Therefore, the kinetics of product formation by the CYP2F1 and CYP2F3 enzymes were compared with other cytochrome P450 enzymes [6].
• The predicted amino acid sequence of CYP2F3 possessed 82% identity to both human CYP2F1 and mouse CYP2F2 [7].
• Therefore, CYP2F1 in human bronchial epithelial lung cells may bioactivate 3MI to 3-methyleneindolenine, which induces programmed cell death at relatively low concentrations [8].

Anatomical context of CYP2F1

• CYP2F1, 4B1, 4F8, 11s (11A, 11B1, and 11B2), 19, and 24 mRNA levels were the highest in the lung, lung, prostate, adrenal gland, placenta, and kidney, respectively; however, the mRNA expression of these eight CYP isoforms in the liver was not detected by this method [9].
• Benzene metabolism in human lung cell lines BEAS-2B and A549 and cells overexpressing CYP2F1 [10].
• We have developed a method using liquid chromatography/mass spectrometry (LC/MS) to evaluate the kinetics of the rates of production of conjugate [C] by recombinant CYP2E1 and CYP2F enzymes and lung microsomes [11].
• Immunisation with one of C1, C2F1, C2F2, or C2F3 caused milder arthritis, even though each of the fragments carried T cell epitopes [12].

Associations of CYP2F1 with chemical compounds

• Remarkable product preferences between the desaturation pathway to form the methyleneindolenine by CYP2F1 and the ring epoxidation pathway to form the oxindole by CYP1A2, were observed [13].
• Human CYP2F1 bioactivates 3-methylindole (3MI), while mouse CYP2F2 bioactivates naphthalene [7].
• The enzyme, however, lacked catalytic activity with other common P450 substrates including 7-ethoxycoumarin, a substrate for CYP2F1, indicating that the substrate selectivity of CYP2F3 appears to be high [7].
• The use of the CYP2E1-selective inhibitor diethyldithiocarbamate and the CYP2F2-selective inhibitor 5-phenyl-1-pentyne demonstrated that both CYP2E1 and CYP2F1 are important in benzene metabolism in the BEAS-2B and A549 human lung cell lines [10].
• Bioactivation of naphthalene to its pneumotoxic epoxide by CYP2F1 was also demonstrated [14].

Other interactions of CYP2F1

• CYP1A1 levels were approximately an order of magnitude lower (3.9 x 10(4) molecules/microg total RNA), followed by CYP2F1 and CYP3A levels that were near the detection limit of the assay [15].
• Using RT-PCR analysis, basal expression of mRNAs coding for CYP2B7, CYP2F1 and CYP2E1 were detected in cultures from several donors [16].
• Compared to other divisions of the CYP2 gene family, the CYP2F subfamily is unusual in having few genes per species and in being selectively expressed in lung tissues [17].

Analytical, diagnostic and therapeutic context of CYP2F1

• On the basis of Southern blotting analysis with multiple restriction enzymes, we conclude that the CYP2F1 gene is flanked by a second highly similar gene [18].
• Localization of CYP2F1 by multipoint linkage analysis and pulsed-field gel electrophoresis [5].

References