Disease relevance of Cyp4ae1

• Relation between the somatic toxicity of dimethylnitrosamine and a genetically determined variation in the level and induction of cytochrome P450 in Drosophila melanogaster [1].

High impact information on Cyp4ae1

• Using the Somatic Mutation And Recombination Test (SMART) we have demonstrated that transgenic larvae expressing the P450 are hypersensitive to the anticancer drug cyclophosphamide, a procarcinogenic substrate which is activated by the enzyme [2].
• In this study we have used precise genetic mapping to identify a mechanism of lufenuron resistance: the overexpression of the cytochrome P450 gene Cyp12a4 [3].
• Shade is the Drosophila P450 enzyme that mediates the hydroxylation of ecdysone to the steroid insect molting hormone 20-hydroxyecdysone [4].
• The present data show that the wild-type genes of two members of the Halloween family of embryonic lethals, disembodied (dib) and shadow (sad), code for mitochondrial cytochromes P450 that mediate the last two hydroxylation reactions in the ecdysteroidogenic pathway in Drosophila, namely the C22- and C2-hydroxylases [5].
• Five different enzymatic activities, catalyzed by both microsomal and mitochondrial cytochrome P450 monooxygenases (CYPs), are strongly implicated in the biosynthesis of ecdysone (E) from cholesterol [5].

Biological context of Cyp4ae1

• The genetic map of the distribution of D. melanogaster P450 genes shows (a) the absence of P450 genes on the chromosome 4 and Y, (b) more than half of the P450 genes are found on chromosome 2, and (c) the largest cluster contains nine genes [6].
• Of these 90 P450 sequences, 83 code for apparently functional genes whereas seven are apparent pseudogenes [6].
• The cytochrome P450 gene superfamily is represented by 90 sequences in the Drosophila melanogaster genome [6].
• The cytochrome P450 gene superfamily in Drosophila melanogaster: annotation, intron-exon organization and phylogeny [6].
• Cytochrome P450 gene clusters in Drosophila melanogaster [7].

Anatomical context of Cyp4ae1

• Furthermore, analysis of c/ebp beta-deficient mice shows that mutant animals are defective in expression of a murine CYP2D5 homolog in hepatic cells, confirming the selective ability of C/EBP beta to activate this liver-specific P-450 gene in vivo [8].
• Immunoblot analyses of mature and regressed corpora lutea indicated a parallel expression of Ad4BP and side-chain cleavage P-450, and both proteins significantly decreased in the regressed tissues [9].
• Formation of 2-bromoacrolein (2BA) from tris(2,3-dibromopropyl)phosphate (Tris-BP) by cytochrome P450 (cyt. P450) activity is most likely responsible for the high mutagenicity of Tris-BP for bacteria in vitro when rat liver microsomes are used for metabolic activation [10].
• In contrast, increases in the rate of BP turnover per molecule of cytochrome P-450, intensity of the hemoprotein band with apparent molecular weight 56,000 and the yield of BP 7,8-dihydrodiol and 9,10-dihydrodiol occurred only in microsomes of BP-pretreated 364yv flies but not of Turku ones [11].
• Feeding of these compounds in combination with the inhibition of cytochrome P-450 by 1-phenylimidazole (PhI) allowed sufficient quantities of the mutagen to reach the gonads and to produce significant genetic damage [12].

Associations of Cyp4ae1 with chemical compounds

• The concentrations of these labdane diterpenes required to elicit a 50% inhibition of the cytochrome P-450 dependent steroid hydroxylase activity in the insect tissues ranged from approximately 5 x 10(-6) to 5 x 10(-4) M [13].
• Effects of the adenylate cyclase activator forskolin and its inactive derivative 1,9-dideoxyforskolin on insect cytochrome P-450 dependent steroid hydroxylase activity [13].
• Waters and colleagues recently suggested [Waters, L. C., Zelhof, A. C., Shaw, B. J. & Ch'ang, L.-Y. (1992) Proc. Natl. Acad. Sci. USA 89, 4855-4859] that an insertion of a long terminal repeat of transposable element 17.6 into the 3' untranslated region of a P450 gene leads to susceptibility to the insecticide DDT in Drosophila melanogaster [14].
• However, there is some controversy as to how the second step of the reaction, from NHA to NO and L-citrulline, occurs within the P450 domain of NOS [15].
• P450-dependent bioactivation of Tris-BP [10].

Analytical, diagnostic and therapeutic context of Cyp4ae1

• Sequence alignments were used to draw phylogenetic trees and to analyze the intron-exon organization of each functional P450 gene [6].
• Twelve cytochrome P450 cDNA fragments were cloned from Drosophila melanogaster by reverse transcriptase/PCR (RT/PCR) using degenerate oligonucleotide primers [7].
• P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature [16].
• The use of a degenerate PCR primer targeted to the haem-binding decapeptide unique to the cytochrome P450 superfamily resulted in the identification of 14 novel cytochrome P450s in the Mediterranean Fruit Fly, Ceratitis capitata [17].
• Although the chromosome 2 locus was not associated with a significant increase in cytochrome P-450 content, SDS polyacrylamide gel electrophoresis of microsomal proteins detected increased silver staining of a polypeptide having a relative molecular mass (Mr) of about 52,000 [18].

References