Cytochrome Cyplal

A study of the modulation of benzo(a-)pyrene metabolism and regulation of cytochrome CYPlAl gene expression by piperine in 5 L cells in culture revealed that piperine-mediated inhibition of AHH activity and consequent suppression of the procarcinogen activation results from direct interaction of piperine with... 

Thirman, M.J. Albrecht, J.H. Kruger, M.A. Ericson, R.R. Cherwitz, D.L. Park, S.S. Gelboin, H.V. Holtzman, J.L. 1994. Induction of cytochrome CYPlAl and formation of toxic metabolites of benzo[a]pyrene by rat aorta a possible role in atherogenesis. 

Carotenoid oxidation products are also supposed to have detrimental effects in vivo. As mentioned earlier, they are suspected to be involved in the adverse effects of high doses of 3-carotene supplementation in smokers and asbestos workers (CARET and ATBC studies) and in smoke-exposed ferrets. The mechanisms potentially involved have been investigated in vitro. P-Apo-8 -carotenal, an eccennic cleavage oxidation product of P-carotene, was shown to be a strong inducer of CYPlAl in rats, whereas P-carotene was not active. Cytochrome P450 (CYP 450) enzymes thus induced could enhance the activation of carcinogens and the destruction of retinoic acid. ... 

Meyer RP, Podvinec M, Meyer UA. 2002. Cytochrome P450 CYPlAl accumulates in the cytosol of kidney and brain and is activated by heme. Mol Pharmacol 62 1061-1067. 

Metabolic competence of HepG2 human hepatoblastoma cells depends on the source and culture conditions. They have both Phase I and II metabolizing enzymes. Cytochrome P450 enzymes are found in much lower levels in HepG2 cells than in primary human hepatocytes but many of these enzymes are inducible, including CYPlAl, 1A2, 2B6, 2E1 and 3A4. The latter metabolizes approximately 50% of drugs currently on the market [32]. 

It is of interest that studies with cloned human cytochromes P450 expressed in insect SF9 cells have shown that only CYP2A6 catalysed 7-hydroxylation, while the formation of orl/20-hydroxyphenylacetaldehyde was supported by CYPlAl, 1A2, 2B6, 2E1 and 3A4 (Zhuo et al, 1999). 

Initial binding of a PBB congener to the Ah receptor is followed by an activation or transcription step and subsequent accumulation of occupied nuclear receptor complexes. These complexes interact with a specific DNA sequence in the CYPlAl gene (which regulates the expression of cytochrome P-450IA1... 

The background cytochrome P450 complement of the cell line and the conditions under which these enzymes are expressed. CYPlAl is sometimes expressed in cultured mammalian cells upon treatment with appropriate inducers (Diamond et al., 1980 Crespi et al., 1985). 

A principal attribute of the cytochrome P450 system is the unprecedented broad substrate specificity it displays, which explains its pivotal role in xenobiotic metabolism. It catalyzes efficiently the metabolism of thousands of structurally diverse chemicals with markedly different molecular shape and size. It achieves this very broad substrate specificity by existing as a superfamUy of enzymes. Each family is subdivided further into subfamilies that may contain one or more enzymes. Enzymes that share a structural similarity of at least 40% belong to the same family, which is indicated by Arabic numbers, whereas if the structural similarity exceeds 55%, then they are classified within the same subfamily, which is denoted by capital letters finally, enzymes belonging to the same subfamily are denoted by Arabic numbers. Eor example, the CYPl family comprises two subfamilies, namely CYPIA and CYPIB the former consists of two enzymes, CYPlAl and CYP1A2, whereas within the... 

Although long-term alcohol can induce some cytochrome P4S0 isozymes, such as CYPlAl, CYP1A2 (257), CYP2B1, and CYP2E1 (258), these effects are not relevant to the coumarins, which are mostly metabolized by CYP2C9. 

Catechol estrogens are formed from the naturally occurring estrogens (estradiol-17)S and estrone) in the central nervous system (e.g., hypothalamus and cerebral cortex) and the anterior pituitary and to a lesser extent in other organs. 17)S-Oxidoreductase and cytochrome P450 (CYPlAl and CYPIBI) are enzymes that convert estrogens to catechol metabolites. 

The enzymes primarily responsible for Phase I metabolism of PAHs are (a) the cytochrome P450s (CYPs) CYPlAl, CYP1A2, and CYPIBI, (b) NADPH... 

Shiota, N., Nagasawa, A., Sakaki, T., Yabusaki, Y., and Ohkawa, H. 1994. Herbicide-resistant tobacco plants expressing the fused enzyme between rat cytochrome P4501al (Cyplal) and yeast NADPH-cytochrome P450 oxidoreductase. Plant Physiol., 106, 17-23. 

The 2 CYPIA proteins have been isolated from the livers of a number of animal species, purified, and shown to share extensive structural similarity and to display similar substrate specificity. The human orthologue of CYP1A2 has been isolated from liver and shown to metabolize the same substrates, and to play the same role in carcinogen activation, as the rodent proteins [9]. The human CYPlAl has not been purified but it has been expressed in mammalian cells like the rodent orthologue, it catalyses the oxidation of polycyclic aromatic hydrocarbons and the N-oxidation of aromatic amines [10]. This apparent similarity in substrate specificity between the human and rodent CYPIA proteins would indicate that where CYPIA is involved, toxicological data can, in principle, be extrapolated to man with more confidence. Of the cytochrome P450 proteins so far characterized, the CYPl family appears to be the most conserved within the phylogenetic tree [11]. 

Reiners. J. J. (1993). Suppre,ssion of cytochrome P450 CYPlAl induction in murine hepatoma 1C1C7 celLs by 12-0-tetradccanoylphorbal-13-acetate and inliibitors of protein kinase C. Arch. Biochem. Biophys. 301(2), 449-454. 

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