Disease relevance of Cpr

• Metabolism in lysates of cells infected with recombinant baculovirus was greatly enhanced by the addition of purified housefly NADPH cytochrome P450 reductase and cytochrome b5 [1].
• Relation between the somatic toxicity of dimethylnitrosamine and a genetically determined variation in the level and induction of cytochrome P450 in Drosophila melanogaster [2].

High impact information on Cpr

• 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 [3].
• In this study we have used precise genetic mapping to identify a mechanism of lufenuron resistance: the overexpression of the cytochrome P450 gene Cyp12a4 [4].
• Shade is the Drosophila P450 enzyme that mediates the hydroxylation of ecdysone to the steroid insect molting hormone 20-hydroxyecdysone [5].
• 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 [6].
• 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 [6].

Biological context of Cpr

• CPR is a single copy gene as shown by genomic Southern hybridisation and maps to the cytogenetic map position 26C on the second chromosome [7].
• The cytochrome P450 gene superfamily is represented by 90 sequences in the Drosophila melanogaster genome [8].
• In Drosophila, a number of P450 monooxygenases are involved in the metabolism of foreign chemicals [Dunkov et al. (1996) Cytochrome P450 gene cluster in Drosophila melanogaster, Mol. Gen. Genet. 251, 290-297] [7].
• Of these 90 P450 sequences, 83 code for apparently functional genes whereas seven are apparent pseudogenes [8].
• The largest cDNA of 2471 nucleotides in length contained an open reading frame of 693 amino acids that includes the putative CPR sequence [7].

Anatomical context of Cpr

• 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 [9].
• 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 [10].
• These results indicate that the fat body participates in the P450-mediated metabolism of excess furanocoumarins unmetabolized by the midgut [11].

Associations of Cpr with chemical compounds

• CYP6A8 was produced in Saccharomyces cerevisiae and enzymatically characterized after catalytic activity was reconstituted with D. melanogaster P450 reductase and NADPH [12].
• The purified DmDeltaHO degraded hemin to biliverdin, CO and iron in the presence of reducing systems such as NADPH/cytochrome P450 reductase and sodium ascorbate, although the reaction rate was slower than that of mammalian HOs [13].
• The effect of xenobiotics (phenobarbital and atrazine) on the expression of Drosophila melanogaster CYP genes encoding cytochromes P450, a gene family generally associated with detoxification, was analyzed by DNA microarray hybridization and verified by real-time RT-PCR in adults of both sexes [14].
• Induction of two cytochrome P450 genes, Cyp6a2 and Cyp6a8, of Drosophila melanogaster by caffeine in adult flies and in cell culture [15].
• Drosophila melanogaster CYP6A8, an insect P450 that catalyzes lauric acid (omega-1)-hydroxylation [12].

Other interactions of Cpr

• Partial reconstitution of 7-ethoxycoumarin de-ethylase activity was achieved using rabbit NADPH: cytochrome P450 reductase and purified preparations containing P450-B [16].

Analytical, diagnostic and therapeutic context of Cpr

• Sequence alignments were used to draw phylogenetic trees and to analyze the intron-exon organization of each functional P450 gene [8].
• 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