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Topic: Cytochrome P450 monooxygenase system


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In the News (Tue 14 Feb 12)

  
  Reference.com/Encyclopedia/Cytochrome P450 oxidase
Cytochrome P450 oxidase (abbreviated CYP or CYP450) is a generic term for a large number of evolutionary related oxidative enzymes (EC 1.14) important in animal, plant, and bacterial physiology.
Cytochrome P450 eryF (CYP107A1) originally from the actinomycete bacterium Saccharopolyspora erythraea is responsible for the biosynthesis of the antibiotic erythromycin by C6-hydroxylation of the macrolide 6-deoxyerythronolide B. Cytochrome P450 BM3 (CYP102A1) from the soil bacterium Bacillus megaterium catalyzes the NADPH-dependent hydroxylation of several long-chain fatty acids at the ω–1 through ω–3 positions.
Cytochromes P450 are present in many other tissues of the body including the mucosa of the gastrointestinal tract, and play important roles in hormone synthesis and breakdown (including estrogen and testosterone synthesis and metabolism), cholesterol synthesis, and vitamin D metabolism.
www.reference.com /browse/wiki/Cytochrome_P450_oxidase   (1393 words)

  
 Research Faculty Listings: Shaun Black
The Cytochrome P450 Monooxygenase System is widely-distributed in nature, and serves a variety of important physiological functions.
Both portions of the immune system are inducible, exhibit wide recognition specificity, and serve to protect the organism from damage caused by toxic foreign substances.
Long-term goals of this research are to achieve a clarity of understanding with regard to the P450 monooxygenase system at the molecular level, and through this understanding to impact favorably on solutions to the problems of carcinogenesis and drug-disposition tolerance/toxicity.
psyche.uthct.edu /shaun/SBlack/SBlackFac.html   (843 words)

  
 Pesticides: An Important but Underused Model for the Environmental Health Sciences
In vitro with microsomal systems, this interaction is manifested as a type I binding spectrum with a peak at 390 nm and a trough at 420 nm.
The relative contribution of P450 and FMO in mouse skin to the sulfoxidation of phorate was investigated and compared to that of liver microsomes.
Induction of rat hepatic microsomal cytochrome P450 and aryl hydrocarbon hydroxylase by 1,3-benzodioxole derivatives.
www.herc.org /news/pesticides/hodgson-full.html   (9159 words)

  
 JIS: Tschinkel 2.12.2002
Cytochrome P450s play an important role in metabolism of host plant chemicals, and in degradation of various insecticides such as pyrethroids, organophosphorus compounds, carbamates etc. (Tsukamoto, 1983; Oppenooth, 1985; Scott and Wen, 2001; Andersen et al., 1994).
The effects of cytochrome P450 monooxygenase inhibitors on the toxicity of permethrin in the permethrin-resistant strain of Culex quinquefasciatus have been studied, as well as the quantities of the enzymes and the degradation of permethrin by the enzymes in permethrin-susceptible and resistant strains (Kasai et al., 1998; Zhou et al., 2001; Qiu and Leng, 1999).
The system was kept 94° C for 1 min, then 30 cycles of RT-PCR (94° C for 30 sec, 45° C for 30 sec, 72° C for 1 min), and was finally kept at 72° C for 5 min.
www.insectscience.org /5.45   (1466 words)

  
 Reviews on P450 proteins
Degtyarenko, K.N. and Archakov, A.I. Molecular evolution of P450 superfamily and P450­containing monooxygenase systems.
Lin, J.H. and Lu, A.Y.H. Inhibition and induction of cytochrome P450 and the clinical implications.
Munro, A.W. and Lindsay, J.G. Bacterial cytochromes P­450.
metallo.scripps.edu /promise/P450_REV.html   (2323 words)

  
 Directed Evolution of Cytochrome P450
Cytochrome P450 enzymes (P450s) constitute a superfamily of heme-containing proteins found in bacteria, fungi, plants, and animals.
P450s are monooxygenases that oxidize a vast array of hydrophobic compounds, from simple alkanes to complex endogenous molecules such as steroids and fatty acids.
The evolved alkane P450 hydroxylase was found to have even higher activity on fatty acids, the presumed biological substrates for P450 BM-3, which was already one of the most efficient P450s known.
www.che.caltech.edu /groups/fha/p450.html   (1646 words)

  
 Microsomal P 450 System   (Site not responding. Last check: 2007-10-10)
Experimentally, the ER system is isolated in the microsomal fraction of cell centrifugation and it is also known as the microsomal oxidizing system.
These systems contain a number of different cytochromes known collectively as the cytochrome P450 system (historically, they were first identified by a strong absorption in the visible range at 450 nm).
The P450 system is also involved in the processing of ethanol, especially when there is a high dietary intake (greater than 10-20 % of calories).
www.hscbklyn.edu /SUNY/Biochem/ALCOHOL/alcohol_P450.html   (364 words)

  
 Porter Laboratory Research Projects
Current studies on this system using cell culture, purified enzymes, and subcellular preparations from whole animals may elucidate new mechanisms by which cholesterol synthesis is regulated.
Squalene monooxygenase requires an electron transfer partner as a source of electrons, and this redox partner has traditionally been thought to be NADPH-cytochrome P450 reductase (CPR).
Earlier studies on the coexpression of human cytochrome P450 2E1 with cytochrome P450 reductase in bacteria allowed the generation of an active mammalian monooxygenase system in these microorganisms.
www.uky.edu /Pharmacy/ps/porter   (404 words)

  
 Involvement of a Cytochrome P450 Monooxygenase in Thaxtomin A Biosynthesis by Streptomyces acidiscabies -- Healy et al. ...
Involvement of a Cytochrome P450 Monooxygenase in Thaxtomin A Biosynthesis by Streptomyces acidiscabies -- Healy et al.
Involvement of a Cytochrome P450 Monooxygenase in Thaxtomin A Biosynthesis by Streptomyces acidiscabies
of the best-studied bacterial P450, the P450cam of Pseudomonas
jb.asm.org /cgi/content/full/184/7/2019   (5006 words)

  
 Introduction to cytochromeP450
Cytochromes P450 enzymes constitute a large superfamily of haem-thiolate proteins involved in the metabolism of a wide variety of both exogenous and endogenous compounds.
The cytochrome P450 (CYP) mixed function monooxygenases are located on the smooth endoplasmic reticulum of cells throughout the body, but the highest concentrations are found in the liver (hepatocytes) and small intestine.
Members of the CYP3A subfamily are the most abundant cytochrome enzymes in humans, accounting for 30% of the cytochrome enzymes in the liver and 70% of those in the gut.
vub.vub.ac.be /~fabi/edu/3degraad/HIV/cytochrome.html   (1155 words)

  
 InterPro: IPR001128 Cytochrome P450
Cytochrome P450 enzymes are a superfamily of haem-containing mono-oxygenases that are found in all kingdoms of life, and which show extraordinary diversity in their reaction chemistry.
Cytochrome P450 enzymes use haem to oxidise their substrates, using protons derived from NADH or NADPH to split the oxygen so a single atom can be added to a substrate.
The divergence of the cytochrome P450 superfamily into B- and E-classes, and further divergence into stable clusters within the E-class, appears to be very ancient, occurring before the appearance of eukaryotes.
www.ebi.ac.uk /interpro/IEntry?ac=IPR001128   (3726 words)

  
 John B. Schenkman Faculty Member at the UConn Health Center Graduate School
The structure of cytochrome P450cam (CYP101) is known, and the heme is located under a shallow depression on the proximal surface of the protein.
We have developed heterologous expression systems using Escherichia coli for production of different cytochrome P450 forms in order to determine their properties and their possible involvement in a number of genetic disorders in humans.
We believe it is possible that altered expression of certain forms of cytochrome P450 could cause enhanced growth and development or regions of the skin, as well as influence the inflammatory processes seen with this disease.
grad.uchc.edu /phdfaculty/schenkman.html   (1320 words)

  
 Respiratory Toxicology Core
As a primary interface between the organism and its environment, the respiratory system is the target for a wide range of toxicants including reactive gases, agricultural chemicals, and airborne pathogens and particles.
In mice, post-natal differentiation of the phase II enzyme systems indicate that there is a substantial mismatch in some of these pathways in comparison to the level of bioactivation potential in neonatal animals.
Cytochrome P450 2E1 in rat tracheobronchial airways: response to ozone exposure.
www.envtox.ucdavis.edu /cehs/RESCORE/respirat.htm   (2822 words)

  
 The lung HETEs (and EETs) up -- Jacobs and Zeldin 280 (1): 1 -- AJP - Heart and Circulatory Physiology
The cytochrome P450 monooxygenase system of rabbit lung: enzyme components, activities, and induction in the nonciliated bronchiolar epithelial, alveolar type II cell, and alveolar macrophage.
The effect of substrate on the expression of activity catalyzed by cytochrome P450: metabolism mediated by rabbit isozyme 6 in pulmonary microsomal and reconstituted monooxygenase systems.
Bioactivation of arachidonic acid by cytochrome P450 monooxygenases of guinea pig lung: the orthologue of cytochrome P450 2B4 is solely responsible for formation of epoxyeicosatrienoic acids.
ajpheart.physiology.org /cgi/content/full/280/1/H1   (6642 words)

  
 Herbal-rs   (Site not responding. Last check: 2007-10-10)
Cytochrome p450 enzyme function CYP levels are influenced by intake of prescribed drugs.
The Cytochrome P450 Monooxygenase System The cytochrome P450 enzyme family is the major catalyst of drug biotransformation reactions.
The degree to which cytochrome P450 monooxygenase activity and hepatic elimination are decreased will be a indication of the severity of liver damage.
www.godshaer.co.uk /herbal-rs.php   (6151 words)

  
 Epoxygenase Metabolites of Arachidonic Acid Affect Electrophysiologic Properties of Rat Tracheal Epithelial Cells1 -- ...
Domin BA, Devereux TR and Philpot RM (1986) The cytochrome P450 monooxygenase system of rabbit lung: enzyme components, activities, and induction in the nonciliated bronchiolar epithelial (Clara) cell, alveolar type II cell, and alveolar macrophage.
Knickle LC and Bend J (1994) Bioactivation of arachidonic acid by the cytochrome P450 monooxygenases of guinea pig lung: The orthologue of cytochrome P450 2B4 is solely responsible for formation of epoxyeicosatrienoic acids.
Serabjit-Singh CJ, Nishio SJ, Philpot RM and Plopper CG (1988) The distribution of cytochrome P-450 monooxygenase in cells of the rabbit lung: An ultrastructural immunocytochemical characterization.
jpet.aspetjournals.org /cgi/content/full/286/2/772   (5476 words)

  
 Engineering of a functional human NADH-dependent cytochrome P450 system -- Döhr et al. 98 (1): 81 -- Proceedings ...
NADPH cytochrome P450 reductase (CPR) (EC 1.6.2.4) is a microsomal dual flavin redox protein.
The effect of the mutations on cytochrome c reductase and EROD activity in bacterial membranes is shown in Table 1.
Cytochrome c reduction was measured as described in the legend to Table 1 by using CPR with NADPH (15 µM, filled symbols) or W676A with NADH (300 µM, open symbols).
www.pnas.org /cgi/content/full/98/1/81   (4160 words)

  
 Expression of a soybean cytochrome P450 monooxygenase cDNA in yeast and tobacco enhances the metabolism of phenylurea ...
Expression of a soybean cytochrome P450 monooxygenase cDNA in yeast and tobacco enhances the metabolism of phenylurea herbicides -- Siminszky et al.
Cytochrome P450 monooxygenases (P450s) are ubiquitous hemoproteins present in microorganisms, plants, and animals.
Characterization of Maize Cytochrome P450 Monooxygenases Induced in Response to Safeners and Bacterial Pathogens
www.pnas.org /cgi/content/full/96/4/1750   (4046 words)

  
 Poster B   (Site not responding. Last check: 2007-10-10)
Approaches to generating soluble eukaryotic P450 enzymes have involved removal of the hydrophobic membrane anchor of the P450 by insertion of a Xa protease recognition site (4), expression of N-terminal truncated forms of P450 (5) or introduction of a thrombin sensitive site beyond the membrane anchor and subsequent cutting (6).
Yeast NADPH cytochrome P-450 oxidoreductase lacking 33 amino acids of the N-terminus (7) was over expressed as a water soluble form in Escherichia coli.
P450 interaction with mammalian NADPH cytochrome P450 reductase requires the hydrophobic N-terminus of the reductase (8).
users.aber.ac.uk /cca/p450/post_b.html   (1171 words)

  
 Cytochrome P450: New Nomenclature and Clinical Implications
Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians.
The emerging role of cytochrome P450 3A in psychopharmacology.
Evidence that glucocorticoids and pregnenolone 16 alpha-carbonitrile regulate de novo synthesis of a common form of cytochrome P-450 in cultures of adult rat hepatocytes and in the liver in vivo.
www.aafp.org /afp/980101ap/cupp.html   (4175 words)

  
 2001 , September, Volume 1, Issue 1, p.38-42   (Site not responding. Last check: 2007-10-10)
The ultrastructural changes of plant cells and the activity of the cytochrome P450-containing monooxygenase system under the action of different stress factors have been studied.
It is shown that upon fungal infection cytochrome P450 induction increases.
The results obtained demonstrate that the microsomal monooxygenase system can become incorporated into cellular energy metabolism and hence becomes responsible for adaptational processes, besides its main detoxificational function.
www.amsi.ge /jbpc/010101/010108.html   (145 words)

  
 The Asia Rice Foundation: Bangladesh Rice Articles
The cytochrome P450 monooxygenase (P450) system, consisting of cytochrome P450 and NADPH-cytochrome P450 oxidoreductase, catalyzes monooxygenation of lipophilic xenobiotic compounds, including herbicides.
In the transplanting–cultivation system of rice seedling, standing water in paddies prevents the germination of many weeds, and as a result, few kinds of plants are major weeds.
In the future, transgenic plants expressing P450 species should be good not only for developing herbicide-tolerant rice but also for reducing the environmental impact of agrochemicals.
www.asiarice.org /sections/whatsnew/transgenicrice.htm   (1129 words)

  
 Drug metabolism
Factors responsible for the liver's contribution to drug metabolism include that it is a large organ, that it is the first organ perfused by chemicals absorbed in the gut, and that there are very high concentrations of most drug-metabolizing enzyme systems relative to other organs.
The Cytochrome P450 monooxygenase system is the most important pathway in this regard.
Cytochrome P450 monooxygenase system enzymes can also vary across individuals, with deficiencies occurring in 1 - 30% of people, depending on their ethnic background.
www.mrsci.com /Metabolism/Drug_metabolism.php   (1084 words)

  
 SELECTIVITIES OF HUMAN CYTOCHROME P450 INHIBITORS TOWARD RAT P450 ISOFORMS: STUDY WITH cDNA-EXPRESSED SYSTEMS OF THE ...
Bourrié M, Meunier V, Berger Y, and Fabre G (1996) Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes.
Nedelcheva V and Gut I (1994) P450 in the rat and man: methods of investigation, substrate specificities and relevance to cancer.
Newton DJ, Wang RW, and Lu AYH (1995) Cytochrome P450 inhibitors: Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes.
dmd.aspetjournals.org /cgi/content/full/31/7/833   (2064 words)

  
 Environmental Genome Project Research Activities - p450 Mediated Lung Toxicity in Humans and Monkeys
Among the factors likely to influence the susceptibility of the lung to toxic chemicals are the cellular distribution and catalytic activities of the key metabolic enzymes (cytochrome P450 monooxygenases) which bioactivate inert chemicals to reactive, lung toxic metabolites.
The cellular distribution of P450 isozymes responsible for the bioactivation of lung toxicants in rodents (CYP2B, CYP2E, CYP2F, CYP4B) will be defined in monkey and human lung.
This work should provide a better understanding of the similarities and differences in the biologic response of lungs of rodents, monkeys, and humans to chemicals that undergo metabolic activation by the cytochrome P450 monooxygenase system.
www.niehs.nih.gov /envgenom/abstract/r01-8408.htm   (405 words)

  
 Pharmacokinetics in the Infant
Most enzymatic microsomal systems responsible for drug metabolism are present at birth and their activities increase with advancing gestational and postnatal age (3,12,30-32).
Enzymatic systems responsible for theophylline oxidation and methylation to caffeine are active in premature neonates; whereas, the development of enzymes for oxidative demethylation do not develop for several months of life (34,35).
Recently, caffeine has been identified as a sensitive biomarker for development of the P450 monooxygenase system activity (38) and maturation of this system during critical phases of growth and development could be mapped.
www.ehponline.org /members/1994/Suppl-11/milsap-full.html   (2925 words)

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