Disease relevance of CYP2F1P

• Mutations in many CYP genes cause inborn errors of metabolism and contribute to many clinically relevant diseases [1].
• Cytochrome P450 (CYP) gene transfer sensitizes tumor xenografts to anticancer prodrugs such as cyclophosphamide (CPA) without a detectable increase in host toxicity [2].
• Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response to pulse cyclophosphamide in lupus nephritis [3].
• CONCLUSION: Determination of selected cytochrome P450 enzyme genotypes may be valuable for predicting the risk of premature ovarian failure in lupus nephritis patients treated with cyclophosphamide [3].
• In human endothelial cells, hypoxia enhanced the activity of the CYP 2C9 promoter, increased the expression of CYP 2C mRNA and protein and augmented 11,12-EET production [4].

Psychiatry related information on CYP2F1P

• Elevated hepatic and depressed renal cytochrome P450 activity in the Tg2576 transgenic mouse model of Alzheimer's disease [5].
• Acceleration of methadone metabolism caused by cytochrome P450 (CYP) 3A4 induction by antiretroviral drugs or rifampicin (rifampin) has caused methadone withdrawal symptoms [6].
• The involvement of cytochrome P450 (CYP) enzymes in olfaction has been demonstrated in vertebrates over the past decade [7].
• Dose-dependent alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 3 weeks have indicated that increase in cytochrome P450 activity may lead to the accumulation of deltamethrin and its metabolites to the levels that may be sufficient to alter the behavioral activity of the offspring [8].
• CYP testing has applications in toxicology and absorption, distribution, metabolism and excretion (ADME) profiling as a guide to drug development.AmpliChip CYP450 may be used in conjunction with pharmacotherapy to guide decision making about selection of drugs and dosage [9].

High impact information on CYP2F1P

• Cytochrome P450 enzymes are heme-containing monooxygenases that are named after an absorption band at 450 nm when complexed with carbon monoxide [10].
• Except for 24, 25-epoxysterols, most oxysterols arise from cholesterol by autoxidation or by specific microsomal or mitochondrial oxidations, usually involving cytochrome P-450 species [11].
• The MEOS was purified and reconstituted using 2E1, phospholipids, and cytochrome P-450 reductase and shown to oxidize ethanol to acetaldehyde, mainly as a monooxygenase and secondarily via hydroxyl radicals, with transcriptional and posttranscriptional regulation [12].
• Haplotype block structure of the cytochrome P450 CYP2C gene cluster on chromosome 10 [13].
• The Cyp26a1 (cytochrome p450, 26) protein metabolizes retinoic acid into more polar hydroxylated and oxidized derivatives [14].

Chemical compound and disease context of CYP2F1P

• Interactive effect of cytochrome P450 17alpha-hydroxylase and dopamine D3 receptor gene polymorphisms on abnormal involuntary movements in chronic schizophrenia [15].
• Cytochrome P450 and arachidonic acid metabolites: role in myocardial ischemia/reperfusion injury revisited [16].
• Therefore, the authors investigated the protein expression of Glutathione S-transferase (GST) isoforms and cytochrome P450 (CYP) known to be involved in the metabolism of steroid hormones and endogenous as well as exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression [17].
• Several lines of data support the possibility that certain CYP metabolites resulting from the hydroxylation of AA such as 20-hydroxyeicosatetraenoic acid (20-HETE) are potent vasoconstrictors and may produce detrimental effects in the heart during ischemia and pro-inflammatory effects during reperfusion [16].
• METHODS AND RESULTS: Sixteen patients with congestive heart failure (New York Heart Association classes II-IV) received a metabolic probe cocktail consisting of caffeine, mephenytoin, dextromethorphan, and chlorzoxazone to assess the activities of the CYP enzymes 1A2, 2C19, 2D6, and 2E1 [18].

Biological context of CYP2F1P

• Transfection of coronary arteries with CYP 2C8/34 antisense oligonucleotides results in decreased levels of CYP 2C and attenuates EDHF-mediated vascular responses [19].
• Cytochrome P450 (CYP) enzymes in extrahepatic tissues often play a dominant role in target tissue metabolic activation of xenobiotic compounds [20].
• Cytochrome P-450 4F18 is the leukotriene B4 omega-1/omega-2 hydroxylase in mouse polymorphonuclear leukocytes: identification as the functional orthologue of human polymorphonuclear leukocyte CYP4F3A in the down-regulation of responses to LTB4 [21].
• Recent studies suggest that cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids (EETs) elicit cell proliferation and promote angiogenesis [4].
• BACKGROUND: Components of grapefruit juice may impair the activity of intestinal cytochrome P450 (CYP) 3A enzymes, sometimes resulting in clinically important drug interactions [22].

Anatomical context of CYP2F1P

• Cytochrome P450 2C is an EDHF synthase in coronary arteries [19].
• Of particular interest are the preferential expression of certain CYPs in the respiratory tract and the regional differences in CYP expression profile in different parts of the gastrointestinal tract [20].
• Cytochrome P450 regulation by hepatocyte nuclear factor 4 in human hepatocytes: a study using adenovirus-mediated antisense targeting [23].
• Cytochrome P450 epoxygenases 2C8 and 2C9 are implicated in hypoxia-induced endothelial cell migration and angiogenesis [4].
• Increased cytochrome P450 17alpha-hydroxylase promoter function in theca cells isolated from patients with polycystic ovary syndrome involves nuclear factor-1 [24].

Associations of CYP2F1P with chemical compounds

• Here we show that the induction of cytochrome P450 (CYP) 2C8/34 in native porcine coronary artery endothelial cells by beta-naphthoflavone enhances the formation of 11,12-epoxyeicosatrienoic acid, as well as EDHF-mediated hyperpolarization and relaxation [19].
• The anticancer oxazaphosphorine prodrugs cyclophosphamide and ifosfamide are activated in human liver by a 4-hydroxylation reaction catalyzed by multiple cytochrome P450 (CYP) enzymes [25].
• Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines [25].
• Matrix metalloprotease (MMP) activity was increased in CYP-2C9-overexpressing cells and correlated with increased invasion through Matrigel-coated Transwell chambers: an effect sensitive to the CYP 2C9 inhibitor sulfaphenazole as well as to EEZE and the MMP inhibitor GM6001 [4].
• Cytochrome P 450 17alpha-hydroxylase activity has been implicated with modulation of central dopamine release as well as neuroprotection [15].

Regulatory relationships of CYP2F1P

• In the current study CYP2E1 knockout mice and wild-type controls were used to further examine the cytochrome P450 isozymes involved in metabolism of 24 microM benzene [26].

Other interactions of CYP2F1P

• The CYP2F1 gene encodes a cytochrome P450 enzyme capable of bioactivating a number of pulmonary-selective toxicants [27].
• In this investigation, studies were undertaken to test the hypothesis that TCE metabolism to chloral hydrate (CH) is mediated by cytochrome P450 enzymes, including CYP2E1, CYP2F, and CYP2B1 [28].

Analytical, diagnostic and therapeutic context of CYP2F1P

• CYP was isolated from the reduction samples, and the P450 profiles on Western blots were compared with the RT-PCR results [29].
• Characterization of cytochrome P450 enzymes in human breast tissue from reduction mammaplasties [29].
• The structural and functional aspects of cytochrome P450 (CYP) enzymes are reviewed in the light of current developments in X-ray crystallography and other physical evidence, together with recent findings on the regulation of, and polymorphisms in, the human drug-metabolizing CYPs [30].
• Cytochrome P450 (CYP) of the 3A family (CYP3A) has been detected in minipig liver microsomes by immunochemical screening (Western blotting), revealing bands that co-migrate with human CYP3A4 and 3A5 [31].
• Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction [32].

References