scholarly journals Cytochrome P450 in GtoPdb v.2021.2

2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
Kathryn Burns ◽  
Nuala Ann Helsby
Keyword(s):  
Cytochrome P450 ◽  
Drug Disposition ◽  
Cytochrome P450 Enzyme ◽  
Multiple Substrates ◽  
Cyp Enzymes ◽  
Physiological Processes ◽  
Enzyme Superfamily ◽  
P450 Enzyme ◽  
The Individual ◽  
Fat Soluble Vitamins

The cytochrome P450 enzyme superfamily (CYP), E.C. 1.14.-.-, are haem-containing monooxygenases with a vast range of both endogenous and exogenous substrates. These include sterols, fatty acids, eicosanoids, fat-soluble vitamins, hormones, pesticides and carcinogens as well as drugs. Listed below are the human enzymes, their relationship with rodent CYP enzyme activities is obscure in that the species orthologue may not metabolise the same substrates. Some of the CYP enzymes located in the liver are particularly important for drug metabolism, both hepatic and extrahepatic CYP enzymes also contribute to patho/physiological processes. Genetic variation of CYP isoforms is widespread and likely underlies a proportion of individual variation in drug disposition. The superfamily has the root symbol CYP, followed by a number to indicate the family, a capital letter for the subfamily with a numeral for the individual enzyme. Some CYP are able to metabolise multiple substrates, others are oligo- or mono- specific.

scholarly journals Cytochrome P450 (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Kathryn Burns ◽  
Nuala Ann Helsby
Keyword(s):  
Cytochrome P450 ◽  
Enzyme Activities ◽  
Significant Proportion ◽  
Cytochrome P450 Enzyme ◽  
Physiological Processes ◽  
P450 Enzyme ◽  
The Individual ◽  
Fat Soluble Vitamins ◽  
Extensive Family ◽  
Cyp450 Enzyme

The cytochrome P450 enzyme family (CYP450), E.C. 1.14.-.-, were originally defined by their strong absorbance at 450 nm due to the reduced carbon monoxide-complexed haem component of the cytochromes. They are an extensive family of haem-containing monooxygenases with a huge range of both endogenous and exogenous substrates. These include sterols, fat-soluble vitamins, pesticides and carcinogens as well as drugs. The substrates of some orphan CYP are not known. Listed below are the human enzymes; their relationship with rodent CYP450 enzyme activities is obscure in that the species orthologue may not catalyse the metabolism of the same substrates. Although the majority of CYP450 enzyme activities are concentrated in the liver, the extrahepatic enzyme activities also contribute to patho/physiological processes. Genetic variation of CYP450 isoforms is widespread and likely underlies a significant proportion of the individual variation to drug administration.

Metabolism and mechanism of human cytochrome P450 enzyme 1A2

2021 ◽  
Vol 21 ◽  
Author(s):  
Jingchao Guo ◽  
Xiaohui Zhu ◽  
Sara Badawy ◽  
Awais Ihsan ◽  
Zhenli Liu ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Aromatic Hydrocarbon ◽  
Personalised Medicine ◽  
Cytochrome P450 Enzyme ◽  
Cyp Enzymes ◽  
Human Cytochrome ◽  
P450 Enzyme ◽  
Metabolic Mechanism ◽  
Clinical Drugs ◽  
Human Cytochrome P450 Enzyme

Abstract: Human cytochrome P450 enzyme 1A2 (CYP1A2) is one of the most important cytochrome P450 (CYP) enzymes in the liver, accounting for 13% to 15% of hepatic CYP enzymes. CYP1A2 metabolises many clinical drugs, such as phenacetin, caffeine, clozapine, tacrine, propranolol, and mexiletine. CYP1A2 also metabolises certain precarcinogens such as aflatoxins, mycotoxins, nitrosamines, and endogenous substances such as steroids. The regulation of CYP1A2 is influenced by many factors. The transcription of CYP1A2 involves not only the aromatic hydrocarbon receptor pathway, but also many additional transcription factors, and CYP1A2 expression may be affected by transcription coactivators and compression factors. Degradation of CYP1A2 mRNA and protein, alternative splicing, RNA stability, regulatory microRNAs, and DNA methylation are also known to affect the regulation of CYP1A2. Many factors can lead to changes in the activity of CYP1A2. Smoking, polycyclic aromatic hydrocarbon ingestion, and certain drugs (e.g., omeprazole) increase its activity, while many clinical drugs such as theophylline, fluvoxamine, quinolone antibiotics, verapamil, cimetidine, and oral contraceptives can inhibit CYP1A2 activity. Here, we review the drugs metabolised by CYP1A2, the metabolic mechanism of CYP1A2, and various factors that influence CYP1A2 metabolism. The metabolic mechanism of CYP1A2 is of great significance in the development of personalised medicine and CYP1A2 target-based drugs.

CYTOCHROME P450: Nature's Most Versatile Biological Catalyst

2005 ◽  
Vol 45 (1) ◽  
pp. 1-25 ◽  
Author(s):  
Minor J. Coon
Keyword(s):  
Cytochrome P450 ◽  
Enzyme System ◽  
Cytochrome P450 Enzyme ◽  
Purification And Characterization ◽  
P450 Enzyme ◽  
Microsomal Membranes ◽  
Cytochrome P450 Enzyme System ◽  
The Individual ◽  
Reaction Cycles

The author describes studies that led to the resolution and reconstitution of the cytochrome P450 enzyme system in microsomal membranes. The review indicates how purification and characterization of the cytochromes led to rigorous evidence for multiple isoforms of the oxygenases with distinct chemical and physical properties and different but somewhat overlapping substrate specificities. Present knowledge of the individual steps in the P450 and reductase reaction cycles is summarized, including evidence for the generation of multiple functional oxidants that may contribute to the exceptional diversity of the reactions catalyzed.

Assessment of 25CYP2D6alleles found in the Chinese population on propafenone metabolism in vitro

2016 ◽  
Vol 94 (8) ◽  
pp. 895-899 ◽  
Author(s):  
Ying Su ◽  
Bing-qing Liang ◽  
Yan-lin Feng ◽  
Yunyun Zhan ◽  
Ermin Gu ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Spodoptera Frugiperda ◽  
Expression System ◽  
Ultra Performance Liquid Chromatography ◽  
Intrinsic Clearance ◽  
Cytochrome P450 Enzyme ◽  
Signal Collection ◽  
Enzyme Superfamily ◽  
P450 Enzyme

Cytochrome P450 enzyme 2D6 (CYP2D6) is an important member of the cytochrome P450 enzyme superfamily, with more than 100 CYP2D6 allelic variants being previously reported. The aim of this study was to assess the catalytic characteristics of 25 alleles (CYP2D6.1 and 24 CYP2D6 variants) and their effects on the metabolism of propafenone in vitro. Twenty-five CYP2D6 alleles were expressing in 21 Spodoptera frugiperda (Sf) insect cells, and each variant was evaluated using propafenone as the substrate. Reactions were performed at 37 °C with 1–100 μmol/L propafenone for 30 min. After termination, the product 5-OH-propafenone was extracted and used for signal collection by ultra-performance liquid chromatography (UPLC). Compared with wild type CYP2D6.1, the intrinsic clearance (Vmaxand Km) values of all variants were significantly altered. Three variants (CYP2D6.87, CYP2D6.90, CYP2D6.F219S) exhibited markedly increased intrinsic clearance values (129% to 165%), whereas 21 variants exhibited significantly decreased values (16% to 85%) due to increased Kmand (or) decreased Vmaxvalues. These results indicated that the majority of tested alleles had significantly altered catalytic activity towards propafenone hydroxylation in this expression system. Attention should be paid to subjects carrying these rare alleles when treated with propafenone.

The role of cytochrome P450 enzyme genetic variants in cannabis hyperemesis syndrome—A case report

2021 ◽  
Author(s):  
Maxim Kuzin ◽  
Franziskos Xepapadakos ◽  
Isabel Scharrer ◽  
Marc Augsburger ◽  
Chin‐Bin Eap ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Case Report ◽  
Genetic Variants ◽  
Cytochrome P450 Enzyme ◽  
P450 Enzyme ◽  
Cannabis Hyperemesis Syndrome

Inter-species comparisons of hepatic cytochrome P450 enzyme levels in male ruminants

2003 ◽  
Vol 77 (10) ◽  
pp. 555-560 ◽  
Author(s):  
Miroslav Machala ◽  
Pavel Soucek ◽  
Jir� Neca ◽  
Robert Ulrich ◽  
Jir� Lamka ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzyme ◽  
P450 Enzyme ◽  
Species Comparisons ◽  
Hepatic Cytochrome

scholarly journals Glutathione S-Transferases and Cytochrome P450 Enzyme Expression in Patients with Intracranial Tumors: Preliminary Report of 55 Patients

2018 ◽  
Vol 28 (1) ◽  
pp. 56-62
Author(s):  
Cahit Kural ◽  
Arzu Kaya Kocdogan ◽  
Gulcin Güler Şimşek ◽  
Serpil Oğuztüzün ◽  
Pınar Kaygın ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Brain Tissue ◽  
Pituitary Adenomas ◽  
Normal Brain ◽  
Cytochrome P450 Enzyme ◽  
Intracranial Tumors ◽  
Glutathione S Transferase ◽  
Normal Brain Tissue ◽  
Tissue Samples ◽  
P450 Enzyme

Objective: Intracranial tumors are one of the most frightening and difficult-to-treat tumor types. In addition to surgery, protocols such as chemotherapy and radiotherapy also take place in the treatment. Glutathione S-transferase (GST) and cytochrome P450 (CYP) enzymes are prominent drug-metabolizing enzymes in the human body. The aim of this study is to show the expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 in different types of brain tumors and compare our results with those in the literature. Subjects and Methods: The expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 was analyzed using immunostaining in 55 patients with intracranial tumors in 2016–2017. For GST and CYP expression in normal brain tissue, samples of a portion of surrounding normal brain tissue as well as a matched far neighbor of tumor tissue were used. The demographic features of the patients were documented and the expression results compared. Results: The mean age of the patients was 46.72 years; 29 patients were female and 26 were male. Fifty-seven specimens were obtained from 55 patients. Among them, meningioma was diagnosed in 12, metastases in 12, glioblastoma in 9, and pituitary adenoma in 5. The highest GSTP1, GSTM1, and CYP­1A1 expressions were observed in pituitary adenomas. The lowest GSTP1 expression was detected in glioblastomas and the lowest CYP1B1 expression in pituitary adenomas. Conclusion: GSTP1 and CYP expression is increased in intracranial tumors. These results should be confirmed with a larger series and different enzyme subtypes.

Drug Interactions of Macrolides: Emphasis on Dirithromycin

1997 ◽  
Vol 31 (3) ◽  
pp. 349-356 ◽  
Author(s):  
Vish S Watkins ◽  
Ron E Polk ◽  
Jennifer L Stotka
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Ethinyl Estradiol ◽  
Enzyme System ◽  
Cytochrome P450 Enzyme ◽  
Cytochrome P450 Enzymes ◽  
Kidney Transplant Recipients ◽  
P450 Enzyme ◽  
Cytochrome P450 Enzyme System ◽  
Clinically Significant

Objective To describe the drug interactions of dirithromycin, a new macrolide, and to compare them with those of other macrolides. Data Sources A literature search was performed using MEDLINE to identify articles published between January 1980 and July 1995 concerning the drug interactions of macrolides. Published abstracts were also examined. All studies using dirithromycin were performed under the sponsorship of Eli Lilly and Company. Data Synthesis Erythromycin, the first macrolide discovered, is metabolized by the cytochrome P450 enzyme system. By decreasing their metabolism, erythromycin can interact with other drugs metabolized by the cytochrome P450 enzymes. The lack of such interactions would be a desirable feature in a newer macrolide. We describe studies performed to detect any interactions of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, and ethinyl estradiol. The studies showed that dirithromycin, like azithromycin, is much less likely to cause the interactions detected with clarithromycin and erythromycin. A review of the literature showed differences among macrolides in their abilities to inhibit cytochrome P450 enzymes and, thus, to cause drug–drug interactions. Erythromycin and clarithromycin inhibit cytochrome P450 enzymes, and have been implicated in clinically significant interactions. Azithromycin and dirithromycin neither inhibit cytochrome P450 enzymes nor are implicated in clinically significant drug–drug interactions. Conclusions Dirithromycin, a new macrolide, does not inhibit the cytochrome P450 enzyme system. The concomitant use of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, or ethinyl estradiol was studied in pharmacokinetic and pharmacodynamic studies. In vitro, dirithromycin did not bind cytochrome P450. In healthy subjects, erythromycin increases the clearance of cyclosporine by 51%, whereas dirithromycin causes no significant changes in the pharmacokinetics of cyclosporine. In kidney transplant recipients, administration of dirithromycin was associated with a significant (p < 0.003) decrease of 17.4% in the clearance of cyclosporine. In patients taking low-dose estradiol, the administration of dirithromycin caused a significant (p < 0.03) increase of 9.9% in the clearance of ethinyl estradiol; escape ovulation did not occur. Unlike erythromycin and clarithromycin, dirithromycin had no significant effects on the pharmacokinetics of theophylline, terfenadine, or warfarin. The alterations typical of drug interactions that are based on inhibition of the cytochrome P450 system occurring with erythromycin and clarithromycin were not observed with dirithromycin.

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