CYTOCHROME P450: Structure-Function
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Identification and Developmental Expression of the Full Complement Of
Goldstone et al. BMC Genomics 2010, 11:643 http://www.biomedcentral.com/1471-2164/11/643 RESEARCH ARTICLE Open Access Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish Jared V Goldstone1, Andrew G McArthur2, Akira Kubota1, Juliano Zanette1,3, Thiago Parente1,4, Maria E Jönsson1,5, David R Nelson6, John J Stegeman1* Abstract Background: Increasing use of zebrafish in drug discovery and mechanistic toxicology demands knowledge of cytochrome P450 (CYP) gene regulation and function. CYP enzymes catalyze oxidative transformation leading to activation or inactivation of many endogenous and exogenous chemicals, with consequences for normal physiology and disease processes. Many CYPs potentially have roles in developmental specification, and many chemicals that cause developmental abnormalities are substrates for CYPs. Here we identify and annotate the full suite of CYP genes in zebrafish, compare these to the human CYP gene complement, and determine the expression of CYP genes during normal development. Results: Zebrafish have a total of 94 CYP genes, distributed among 18 gene families found also in mammals. There are 32 genes in CYP families 5 to 51, most of which are direct orthologs of human CYPs that are involved in endogenous functions including synthesis or inactivation of regulatory molecules. The high degree of sequence similarity suggests conservation of enzyme activities for these CYPs, confirmed in reports for some steroidogenic enzymes (e.g. CYP19, aromatase; CYP11A, P450scc; CYP17, steroid 17a-hydroxylase), and the CYP26 retinoic acid hydroxylases. Complexity is much greater in gene families 1, 2, and 3, which include CYPs prominent in metabolism of drugs and pollutants, as well as of endogenous substrates. -
Cytochrome P450 Enzymes in Oxygenation of Prostaglandin Endoperoxides and Arachidonic Acid
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 231 _____________________________ _____________________________ Cytochrome P450 Enzymes in Oxygenation of Prostaglandin Endoperoxides and Arachidonic Acid Cloning, Expression and Catalytic Properties of CYP4F8 and CYP4F21 BY JOHAN BYLUND ACTA UNIVERSITATIS UPSALIENSIS UPPSALA 2000 Dissertation for the Degree of Doctor of Philosophy (Faculty of Pharmacy) in Pharmaceutical Pharmacology presented at Uppsala University in 2000 ABSTRACT Bylund, J. 2000. Cytochrome P450 Enzymes in Oxygenation of Prostaglandin Endoperoxides and Arachidonic Acid: Cloning, Expression and Catalytic Properties of CYP4F8 and CYP4F21. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from Faculty of Pharmacy 231 50 pp. Uppsala. ISBN 91-554-4784-8. Cytochrome P450 (P450 or CYP) is an enzyme system involved in the oxygenation of a wide range of endogenous compounds as well as foreign chemicals and drugs. This thesis describes investigations of P450-catalyzed oxygenation of prostaglandins, linoleic and arachidonic acids. The formation of bisallylic hydroxy metabolites of linoleic and arachidonic acids was studied with human recombinant P450s and with human liver microsomes. Several P450 enzymes catalyzed the formation of bisallylic hydroxy metabolites. Inhibition studies and stereochemical analysis of metabolites suggest that the enzyme CYP1A2 may contribute to the biosynthesis of bisallylic hydroxy fatty acid metabolites in adult human liver microsomes. 19R-Hydroxy-PGE and 20-hydroxy-PGE are major components of human and ovine semen, respectively. They are formed in the seminal vesicles, but the mechanism of their biosynthesis is unknown. Reverse transcription-polymerase chain reaction using degenerate primers for mammalian CYP4 family genes, revealed expression of two novel P450 genes in human and ovine seminal vesicles. -
Mining for Oxysterols in Cyp7b1-/- Mouse Brain and Plasma
biomolecules Communication − − Mining for Oxysterols in Cyp7b1 / Mouse Brain and Plasma: Relevance to Spastic Paraplegia Type 5 Anna Meljon 1,2, Peter J. Crick 1, Eylan Yutuc 1 , Joyce L. Yau 3, Jonathan R. Seckl 3, Spyridon Theofilopoulos 1,4 , Ernest Arenas 4, Yuqin Wang 1 and William J. Griffiths 1,* 1 Swansea University Medical School, ILS1 Building, Singleton Park, Swansea SA2 8PP, UK; [email protected] (A.M.); [email protected] (P.J.C.); [email protected] (E.Y.); s.theofi[email protected] (S.T.); [email protected] (Y.W.) 2 Institute for Global Food Security, Queens University Belfast, Stranmillis Road, Belfast BT9 5AG, UK 3 Endocrinology Unit, BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK; [email protected] (J.L.Y.); [email protected] (J.R.S.) 4 Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden; [email protected] * Correspondence: w.j.griffi[email protected]; Tel.: +44-1792-295562 Received: 6 March 2019; Accepted: 2 April 2019; Published: 13 April 2019 Abstract: Deficiency in cytochrome P450 (CYP) 7B1, also known as oxysterol 7α-hydroxylase, in humans leads to hereditary spastic paraplegia type 5 (SPG5) and in some cases in infants to liver disease. SPG5 is medically characterized by loss of motor neurons in the corticospinal tract. In an effort to gain a better understanding of the fundamental biochemistry of this disorder, we have extended our previous profiling of the oxysterol content of brain and plasma of Cyp7b1 knockout (-/-) mice to include, amongst other sterols, 25-hydroxylated cholesterol metabolites. -
Synonymous Single Nucleotide Polymorphisms in Human Cytochrome
DMD Fast Forward. Published on February 9, 2009 as doi:10.1124/dmd.108.026047 DMD #26047 TITLE PAGE: A BIOINFORMATICS APPROACH FOR THE PHENOTYPE PREDICTION OF NON- SYNONYMOUS SINGLE NUCLEOTIDE POLYMORPHISMS IN HUMAN CYTOCHROME P450S LIN-LIN WANG, YONG LI, SHU-FENG ZHOU Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, P. R. China (LL Wang & Y Li) Discipline of Chinese Medicine, School of Health Sciences, RMIT University, Bundoora, Victoria 3083, Australia (LL Wang & SF Zhou). 1 Copyright 2009 by the American Society for Pharmacology and Experimental Therapeutics. DMD #26047 RUNNING TITLE PAGE: a) Running title: Prediction of phenotype of human CYPs. b) Author for correspondence: A/Prof. Shu-Feng Zhou, MD, PhD Discipline of Chinese Medicine, School of Health Sciences, RMIT University, WHO Collaborating Center for Traditional Medicine, Bundoora, Victoria 3083, Australia. Tel: + 61 3 9925 7794; fax: +61 3 9925 7178. Email: [email protected] c) Number of text pages: 21 Number of tables: 10 Number of figures: 2 Number of references: 40 Number of words in Abstract: 249 Number of words in Introduction: 749 Number of words in Discussion: 1459 d) Non-standard abbreviations: CYP, cytochrome P450; nsSNP, non-synonymous single nucleotide polymorphism. 2 DMD #26047 ABSTRACT Non-synonymous single nucleotide polymorphisms (nsSNPs) in coding regions that can lead to amino acid changes may cause alteration of protein function and account for susceptivity to disease. Identification of deleterious nsSNPs from tolerant nsSNPs is important for characterizing the genetic basis of human disease, assessing individual susceptibility to disease, understanding the pathogenesis of disease, identifying molecular targets for drug treatment and conducting individualized pharmacotherapy. -
Supplementary Material
Supplementary Material Table S1: Significant downregulated KEGGs pathways identified by DAVID following exposure to five cinnamon- based phenylpropanoids (p < 0.05). p-value Term: Genes (Benjamini) Cytokine-cytokine receptor interaction: FASLG, TNFSF14, CXCL11, IL11, FLT3LG, CCL3L1, CCL3L3, CXCR6, XCR1, 2.43 × 105 RTEL1, CSF2RA, TNFRSF17, TNFRSF14, CCNL2, VEGFB, AMH, TNFRSF10B, INHBE, IFNB1, CCR3, VEGFA, CCR2, IL12A, CCL1, CCL3, CXCL5, TNFRSF25, CCR1, CSF1, CX3CL1, CCL7, CCL24, TNFRSF1B, IL12RB1, CCL21, FIGF, EPO, IL4, IL18R1, FLT1, TGFBR1, EDA2R, HGF, TNFSF8, KDR, LEP, GH2, CCL13, EPOR, XCL1, IFNA16, XCL2 Neuroactive ligand-receptor interaction: OPRM1, THRA, GRIK1, DRD2, GRIK2, TACR2, TACR1, GABRB1, LPAR4, 9.68 × 105 GRIK5, FPR1, PRSS1, GNRHR, FPR2, EDNRA, AGTR2, LTB4R, PRSS2, CNR1, S1PR4, CALCRL, TAAR5, GABRE, PTGER1, GABRG3, C5AR1, PTGER3, PTGER4, GABRA6, GABRA5, GRM1, PLG, LEP, CRHR1, GH2, GRM3, SSTR2, Chlorogenic acid Chlorogenic CHRM3, GRIA1, MC2R, P2RX2, TBXA2R, GHSR, HTR2C, TSHR, LHB, GLP1R, OPRD1 Hematopoietic cell lineage: IL4, CR1, CD8B, CSF1, FCER2, GYPA, ITGA2, IL11, GP9, FLT3LG, CD38, CD19, DNTT, 9.29 × 104 GP1BB, CD22, EPOR, CSF2RA, CD14, THPO, EPO, HLA-DRA, ITGA2B Cytokine-cytokine receptor interaction: IL6ST, IL21R, IL19, TNFSF15, CXCR3, IL15, CXCL11, TGFB1, IL11, FLT3LG, CXCL10, CCR10, XCR1, RTEL1, CSF2RA, IL21, CCNL2, VEGFB, CCR8, AMH, TNFRSF10C, IFNB1, PDGFRA, EDA, CXCL5, TNFRSF25, CSF1, IFNW1, CNTFR, CX3CL1, CCL5, TNFRSF4, CCL4, CCL27, CCL24, CCL25, CCL23, IFNA6, IFNA5, FIGF, EPO, AMHR2, IL2RA, FLT4, TGFBR2, EDA2R, -
Polyclonal Antibody to CYP7B1 (C-Term) - Aff - Purified
OriGene Technologies, Inc. OriGene Technologies GmbH 9620 Medical Center Drive, Ste 200 Schillerstr. 5 Rockville, MD 20850 32052 Herford UNITED STATES GERMANY Phone: +1-888-267-4436 Phone: +49-5221-34606-0 Fax: +1-301-340-8606 Fax: +49-5221-34606-11 [email protected] [email protected] AP20144PU-N Polyclonal Antibody to CYP7B1 (C-term) - Aff - Purified Alternate names: 25-hydroxycholesterol 7-alpha-hydroxylase, Cytochrome P450 7B1, Oxysterol 7-alpha- hydroxylase Quantity: 0.1 mg Concentration: 0.5 mg/ml Background: P450 enzymes constitute a family of monooxygenase enzymes that are involved in the metabolism of a wide array of endogenous and xenobiotic compounds including cholesterol. CYP8B1 moderates the ratio of cholic acid over chenodeoxycholic acid to control the solubility of cholesterol. P450 cholesterol 7-hydroxylase, CYP7A1, is the rate limiting enzyme of bile acid synthesis in the liver, and its expression is mediated by the bile acid receptor FXR. CYP27A1 catalyzes vitamin D3 25-hydroxylation and is localized to the mitochondria in kidney and liver. CYP7B1 (oxysterol 7-α-hydroxylase) functions as an enzyme in the alternate bile acid synthesis pathway. Specifically, CYP7B1 metabolizes 25-and 27-hydroxycholesterol. The gene encoding human CYP7B1 maps to chromosome 8q21.3. Mutations in the CYP7B1 gene may cause a metabolic defect in bile acid synthesis characterized by elevated urinary bile acid excretion, severe cholestasis, cirrhosis and liver synthetic failure. Uniprot ID: O75881 NCBI: NP_004811 GeneID: 9420 Host: Goat Immunogen: Peptide with sequence C-YPDSDVLFRYKVKS, from the C Terminus of the protein sequence according to NP_004811.1. Format: State: Liquid purified IgG fraction. -
Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain
1 Review 2 Clinical Implications of 20-Hydroxyeicosatetraenoic 3 Acid in the Kidney, Liver, Lung and Brain: An 4 Emerging Therapeutic Target 5 Osama H. Elshenawy 1, Sherif M. Shoieb 1, Anwar Mohamed 1,2 and Ayman O.S. El-Kadi 1,* 6 1 Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton T6G 2E1, AB, Canada; 7 [email protected] (O.H.E.); [email protected] (S.M.S.); [email protected] (A.M.) 8 2 Department of Basic Medical Sciences, College of Medicine, Mohammed Bin Rashid University of 9 Medicine and Health Sciences, Dubai, United Arab Emirates 10 * Correspondence: [email protected]; Tel.: 780-492-3071; Fax: 780-492-1217 11 Academic Editor: Kishor M. Wasan 12 Received: 12 January 2017; Accepted: 15 February 2017; Published: 20 February 2017 13 Abstract: Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important 14 pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels 15 of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed 16 the role of 20-HETE in the kidney, liver, lung, and brain during physiological and 17 pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, 18 metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of 19 preglomerular vascular tone and tubular ion transport. Furthermore, 20-HETE is involved in renal 20 ischemia/reperfusion (I/R) injury and polycystic kidney diseases. The role of 20-HETE in the liver is 21 not clearly understood although it represents 50%–75% of liver CYP-dependent AA metabolism, 22 and it is associated with liver cirrhotic ascites. -
Rare Novel CYP2U1 and ZFYVE26 Variants Identified in Two Pakistani Families with Spastic 2 Paraplegia
1 Rare novel CYP2U1 and ZFYVE26 variants identified in two Pakistani families with spastic 2 paraplegia. 3 Farah Bibi1, Stephanie Efthymiou2, Thomas Bourinaris2, Ambreen Tariq2, SYNaPS Study Group, 4 Faisal Zafar3, Nouzhat Rana3, Vincenzo Salpietro2, Henry Houlden2, Ghazala Kaukab Raja1 5 6 1. University Institute of Biochemistry & Biotechnology, PMAS – Arid Agriculture University, 7 Rawalpindi, 43600, Pakistan 8 2. Department of Neuromuscular disorders, UCL Institute of Neurology, Queen Square, London 9 WC1N 3BG, UK 10 3. Department of Pediatrics, Multan Nishtar Hospital, Multan, 60000, Pakistan. 11 Corresponding author: Prof. Ghazala Kaukab Raja, University Institute of Biochemistry & 12 Biotechnology, PMAS-Arid Agriculture University, Rawalpindi, 43600, Pakistan, 13 [email protected] 14 Keywords: spastic paraplegia, SPG15, SPG56, next generation sequencing, consanguinity 15 Word count: 1894 16 17 Abstract 18 Bakground: Hereditary Spastic paraplegias (HSPs) are a clinically and genetically heterogeneous 19 group of degenerative disorders characterized by progressive spasticity and weakness of the 20 lower limbs. This study aimed to identify causative gene variants in two unrelated 21 consanguineous Pakistani families presented with 2 different forms of HSP. 22 Methods: Whole exome sequencing (WES) was performed in the two families and variants were 23 validated by Sanger sequencing and segregation analysis. 24 Analysis: In family A, a homozygous pathogenic variant in ZFYVE26 was identified in one family. 25 While in family B, a frameshift variant in CYP2U1 was identified in 4 affected individuals 26 presented with clinical features of SPG56. Our study is the first report of ZFYVE26 mutations 27 causing HSP in the Pakistani population and the second report of CYP2U1 in a Pakistani family. -
Essential Role of the Cytochrome P450 CYP4F22 in the Production of Acylceramide, the Key Lipid for Skin Permeability Barrier Formation
Essential role of the cytochrome P450 CYP4F22 in the production of acylceramide, the key lipid for skin permeability barrier formation Yusuke Ohnoa, Shota Nakamichia, Aya Ohkunia, Nozomi Kamiyamaa, Ayano Naoeb, Hisashi Tsujimurab, Urara Yokoseb, Kazumitsu Sugiurac, Junko Ishikawab, Masashi Akiyamac, and Akio Kiharaa,1 aLaboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan; bKao Corporation, Haga-gun, Tochigi 321-3497, Japan; and cDepartment of Dermatology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan Edited by David W. Russell, University of Texas Southwestern Medical Center, Dallas, TX, and approved May 21, 2015 (received for review February 19, 2015) A skin permeability barrier is essential for terrestrial animals, and its lamellae and/or to stabilize the multiple lipid layers. Linoleic impairment causes several cutaneous disorders such as ichthyosis and acid is one of the essential FAs, and its deficiency causes ich- atopic dermatitis. Although acylceramide is an important lipid for the thyosis symptoms resulting from a failure to form normal acyl- skin permeability barrier, details of its production have yet to be de- ceramide (8). Ichthyosis is a cutaneous disorder accompanied termined, leaving the molecular mechanism of skin permeability bar- by dry, thickened, and scaly skin; it is caused by a barrier ab- rier formation unclear. Here we identified the cytochrome P450 gene normality. In patients who have atopic dermatitis, both total CYP4F22 (cytochrome P450, family 4, subfamily F, polypeptide 22) as ceramide levels and the chain length of ceramides are de- the long-sought fatty acid ω-hydroxylase gene required for acylcer- creased, and ceramide composition is altered also (9–11). -
Characterization of the Novel Defective Cyp2c9*24
DMD Fast Forward. Published on March 1, 2007 as DOI: 10.1124/dmd.106.013722 DMD FastThis article Forward. has not been Published copyedited onand Marchformatted. 1, The 2007 final versionas doi:10.1124/dmd.106.013722 may differ from this version. DMD#13722 CHARACTERIZATION OF THE NOVEL DEFECTIVE CYP2C9*24 ALLELE Downloaded from Author’s names: Darja Herman, Vita Dolzan, Magnus Ingelman-Sundberg dmd.aspetjournals.org Institutions: Institute of Biochemistry, Faculty of Medicine, Ljubljana, Slovenia (D.H., V.D.) Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska at ASPET Journals on September 27, 2021 Institute, Stockholm, Sweden (D.H., M.I.-S.) 1 Copyright 2007 by the American Society for Pharmacology and Experimental Therapeutics. DMD Fast Forward. Published on March 1, 2007 as DOI: 10.1124/dmd.106.013722 This article has not been copyedited and formatted. The final version may differ from this version. DMD#13722 Running title: CHARACTERIZATION OF CYP2C9*24 ALLELE Corresponding author: Vita Dolzan, Institute of Biochemistry, Faculty of Medicine, Vrazov trg 2, SI-1000 Ljubljana, Slovenia; phone: +386 1 543 76 69; fax: + 386 1 543 76 41; e-mail: [email protected] Downloaded from No. of text pages: 8 (excluding Title page, Abstract and References) No. of Figures: 3 dmd.aspetjournals.org No. of references: 15 No. of words in the - Abstract: 242 - Introduction: 351 at ASPET Journals on September 27, 2021 - Results and Discussion: 755 Abbreviations: CYP – cytochrome P450, HEK293 – human embryonic kidney cell line 2 DMD Fast Forward. Published on March 1, 2007 as DOI: 10.1124/dmd.106.013722 This article has not been copyedited and formatted. -
CYP2F1 (NM 000774) Human Tagged ORF Clone Product Data
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for RC223097 CYP2F1 (NM_000774) Human Tagged ORF Clone Product data: Product Type: Expression Plasmids Product Name: CYP2F1 (NM_000774) Human Tagged ORF Clone Tag: Myc-DDK Symbol: CYP2F1 Synonyms: C2F1; CYP2F; CYPIIF1 Vector: pCMV6-Entry (PS100001) E. coli Selection: Kanamycin (25 ug/mL) Cell Selection: Neomycin This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 4 CYP2F1 (NM_000774) Human Tagged ORF Clone – RC223097 ORF Nucleotide >RC223097 representing NM_000774 Sequence: Red=Cloning site Blue=ORF Green=Tags(s) TTTTGTAATACGACTCACTATAGGGCGGCCGGGAATTCGTCGACTGGATCCGGTACCGAGGAGATCTGCC GCCGCGATCGCC ATGGACAGCATAAGCACAGCCATCTTACTCCTGCTCCTGGCTCTCGTCTGTCTGCTCCTGACCCTAAGCT CAAGAGATAAGGGAAAGCTGCCTCCGGGACCCAGACCCCTCTCAATCCTGGGAAACCTGCTGCTGCTTTG CTCCCAAGACATGCTGACTTCTCTCACTAAGCTGAGCAAGGAGTATGGCTCCATGTACACAGTGCACCTG GGACCCAGGCGGGTGGTGGTCCTCAGCGGGTACCAAGCTGTGAAGGAGGCCCTGGTGGACCAGGGAGAGG AGTTTAGTGGCCGCGGTGACTACCCTGCCTTTTTCAACTTTACCAAGGGCAATGGCATCGCCTTCTCCAG TGGGGATCGATGGAAGGTCCTGAGACAGTTCTCTATCCAGATTCTACGGAATTTCGGGATGGGGAAGAGA AGCATTGAGGAGCGAATCCTAGAGGAGGGCAGCTTCCTGCTGGCGGAGCTGCGGAAAACTGAAGGCGAGC CCTTTGACCCCACGTTTGTGCTGAGTCGCTCAGTGTCCAACATTATCTGTTCCGTGCTCTTCGGCAGCCG CTTCGACTATGATGATGAGCGTCTGCTCACCATTATCCGCCTTATCAATGACAACTTCCAAATCATGAGC -
Metabolic Activation and Toxicological Evaluation of Polychlorinated Biphenyls in Drosophila Melanogaster T
www.nature.com/scientificreports OPEN Metabolic activation and toxicological evaluation of polychlorinated biphenyls in Drosophila melanogaster T. Idda1,7, C. Bonas1,7, J. Hofmann1, J. Bertram1, N. Quinete1,2, T. Schettgen1, K. Fietkau3, A. Esser1, M. B. Stope4, M. M. Leijs3, J. M. Baron3, T. Kraus1, A. Voigt5,6 & P. Ziegler1* Degradation of polychlorinated biphenyls (PCBs) is initiated by cytochrome P450 (CYP) enzymes and includes PCB oxidation to OH-metabolites, which often display a higher toxicity than their parental compounds. In search of an animal model refecting PCB metabolism and toxicity, we tested Drosophila melanogaster, a well-known model system for genetics and human disease. Feeding Drosophila with lower chlorinated (LC) PCB congeners 28, 52 or 101 resulted in the detection of a human-like pattern of respective OH-metabolites in fy lysates. Feeding fies high PCB 28 concentrations caused lethality. Thus we silenced selected CYPs via RNA interference and analyzed the efect on PCB 28-derived metabolite formation by assaying 3-OH-2′,4,4′-trichlorobiphenyl (3-OHCB 28) and 3′-OH-4′,4,6′-trichlorobiphenyl (3′-OHCB 28) in fy lysates. We identifed several drosophila CYPs (dCYPs) whose knockdown reduced PCB 28-derived OH-metabolites and suppressed PCB 28 induced lethality including dCYP1A2. Following in vitro analysis using a liver-like CYP-cocktail, containing human orthologues of dCYP1A2, we confrm human CYP1A2 as a PCB 28 metabolizing enzyme. PCB 28-induced mortality in fies was accompanied by locomotor impairment, a common phenotype of neurodegenerative disorders. Along this line, we show PCB 28-initiated caspase activation in diferentiated fy neurons.