Cytochromes P450: A Structure-Based Summary of Biotransformations Using Representative Substrates

Brown, Caitlin M.; Reisfeld, Brad; Mayeno, Arthur N.

doi:10.1080/03602530701836662

Cited by 125 publications

(71 citation statements)

References 175 publications

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“…CYP450 activity in cancer cells may lead to the deactivation of antitumour drugs, thereby limiting therapeutic efficacy. The CYP1, CYP2 and CYP3 families are important enzymes that metabolise a significant number of clinically important drugs (73). Aberrant CYP450 enzymatic activity has been detected in a variety of human cancer cell lines and has been shown to contribute to neoangiogenesis, cancer cell migration, tumour growth and metastasis (74-78).…”

Section: P450 Monooxygenases and Their Inhibitors In Cancer Treatmentmentioning

confidence: 99%

Potency of non-steroidal anti-inflammatory drugs in chemotherapy

Hiľovská

Jendželovský

Fedoročko

2014

Molecular and Clinical Oncology

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Section: P450 Monooxygenases and Their Inhibitors In Cancer Treatmentmentioning

confidence: 99%

Potency of non-steroidal anti-inflammatory drugs in chemotherapy

Hiľovská

Jendželovský

Fedoročko

2014

Molecular and Clinical Oncology

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“…The human genome contains 57 predicted CYPs, divided among 18 families and 44 subfamilies [2]. Only three of these families (CYP1, CYP2 and CYP3) are responsible for drug and steroid metabolism, with CYP3A and especially CYP3A4 being the most important in humans [3].…”

Section: Introductionmentioning

confidence: 99%

NHR-176 regulates cyp-35d1 to control hydroxylation-dependent metabolism of thiabendazole in Caenorhabditis elegans

Jones

Flemming

Urwin

2015

Biochemical Journal

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Knowledge of how drugs are metabolized and excreted is an essential component of understanding their fate within and among target and non-target organisms. Thiabendazole (TBZ) was the first benzimidazole (BZ) to be commercially available and remains one of the most important anthelmintic drugs for medical and veterinary use. We have characterized how Caenorhabditis elegans metabolizes and excretes TBZ. We have shown that TBZ directly binds to the nuclear hormone receptor (NHR)-176 and that this receptor is required for the induction by TBZ of the cytochrome P450 (CYP) encoded by cyp-35d1. Further, RNAi inhibition of cyp-35d1 in animals exposed to TBZ causes a reduction in the quantity of a hydroxylated TBZ metabolite and its glucose conjugate that is detected in C. elegans tissue by HPLC. This final metabolite is unique to nematodes and we also identify two P-glycoproteins (PGPs) necessary for its excretion. Finally, we have shown that inhibiting the metabolism we describe increases the susceptibility of C. elegans to TBZ in wild-type and in resistant genetic backgrounds.

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“…Typically, CYPs oxidize a substrate by incorporation of a single oxygen atom, which defines them as monooxygenase-type enzymes. They catalyze hydroxylation, epoxidation, N, S, and O dealkylation, N oxidation, sulfoxidation, dehalogenation, and a number of other more complex reactions (9,27,40). Also, CYP enzymes play a major role in xenobiotic metabolism and in phase I drug metabolism due to the oxidation of exogenous and endogenous chemicals, including drugs and carcinogens (21).…”

mentioning

confidence: 99%

Differential Regulation by Heat Stress of Novel Cytochrome P450 Genes from the Dinoflagellate Symbionts of Reef-Building Corals

Rosic

Pernice

Dunn

et al. 2010

Appl Environ Microbiol

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Exposure to heat stress has been recognized as one of the major factors leading to the breakdown of the coral-alga symbiosis and coral bleaching. Here, we describe the presence of three new cytochrome P450 (CYP) genes from the reef-building coral endosymbiont Symbiodinium (type C3) and changes in their expression during exposure to severe and moderate heat stress conditions. Sequence analysis of the CYP C-terminal region and two conserved domains, the "PERF" and "heme-binding" domains, confirmed the separate identities of the CYP genes analyzed. In order to explore the effects of different heat stress scenarios, samples of the scleractinian coral Acropora millepora were exposed to elevated temperatures incrementally over an 18-h period (rapid thermal stress) and over a 120-h period (gradual thermal stress). After 18 h of gradual heating and incubation at 26°C, the Symbiodinium CYP mRNA pool was approximately 30% larger, while a further 6°C increase to a temperature above the average sea temperature (29°C after 72 h) resulted in a 2-to 4-fold increase in CYP expression. Both rapid heat stress and gradual heat stress at 32°C resulted in 50% to 90% decreases in CYP gene transcript abundance. Consequently, the initial upregulation of expression of CYP genes at moderately elevated temperatures (26°C and 29°C) was followed by a decrease in expression under the greater thermal stress conditions at 32°C. These findings indicate that in the coral-alga symbiosis under heat stress conditions there is production of chemical stressors and/or transcriptional factors that regulate the expression of genes, such as the genes encoding cytochrome P450 monooxygenases, that are involved in the first line of an organism's chemical defense.

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Cytochromes P450: A Structure-Based Summary of Biotransformations Using Representative Substrates

Cited by 125 publications

References 175 publications

Potency of non-steroidal anti-inflammatory drugs in chemotherapy

Potency of non-steroidal anti-inflammatory drugs in chemotherapy

NHR-176 regulates cyp-35d1 to control hydroxylation-dependent metabolism of thiabendazole in Caenorhabditis elegans

Differential Regulation by Heat Stress of Novel Cytochrome P450 Genes from the Dinoflagellate Symbionts of Reef-Building Corals

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