Abstract
Xenobiotic administration can significantly alter forms of hepatic microsomal cytochrome P-450. Individual forms of cytochrome P-450 are known to be increased by agents, such as phenobarbital, 3-methylcholanthrene, β-naphthoflavone and pregnenolone-16α-carbonitrile1–3. Certain chemicals decrease the levels of these isoenzymes by modulating the heme biosynthetic pathway and, thereby, affect the availability of heme and the amount of hepatic cytochrome P-450, e.g. cobaltous chloride4,5. Some agents can act as suicide substrates (i.e., mechanism-based inhibitors) for one or more cytochrome P-450 forms and, thereby, promote catabolic destruction of these cytochrome P-450 species6,7. Derivatives of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) interact rapidly with cytochrome P-450, promote the rapid destruction of hepatic microsomal cytochrome P-450 and lead to the generation in vivo of N-alkyl protoporphyrins which, in turn, inhibit the activity of mitochondrial ferrochelatase, the enzyme catalyzing the last step in heme biosynthesis8–11. The result is a decreased total hepatic microsomal cytochrome P-450 level and a marked hepatic porphyria12,13.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
F. P. Guengerich, Separation and purification of multiple forms of microsomal cytochrome P-450, J. Biol. Chem. 252: 3970 (1977).
D. E. Ryan, P. E. Thomas, D. Korzeniowski and W. Levin, Separation and characterization of highly purified forms of liver microsomal cytochrome P-450 from rats treated with polychlorinated biphenyls, phenobarbital, and 3-methylcholanthrene, J. Biol. Chem. 254: 1365 (1979).
F. P. Guengerich, G. A Dannan, S. T. Wright, M. V. Martin and L. S. Kaminsky, Purification and characterization of liver microsomal cytochromes P-450: electrophoretic, spectral, catalytic, and immunochemical properties and inducibility of eight isozymes isolated from rats treated with phenobarbital or ß-naphthoflavone, Biochemistry 21: 6019 (1982).
T. R. Tephly and P. Hibbeln, The effect of cobalt chloride administration on the synthesis of hepatic microsomal cytochrome P-450, Biochem. Biophys. Res. Commun. 42: 589 (1971).
T. R. Tephly, C. R. Webb, P. Trussler, F. Kniffen, E. Hasegawa and W. Piper, The regulation of heure synthesis related to drug metabolism, Drug Metab. Dispos. 1: 259 (1973).
P. R. Ortiz de Montellano and B. A. Mico, Destruction of cytochrome P-450 by allylisopropylacetamide is a suicidal process, Arch. Biochem. Biophys. 206: 43 (1981).
H. H. Liem, E. F. Johnson and U. Müller-Eberhard, The effect in vivo and in vitro of allylisopropylacetamide on the content of hepatic microsomal cytochrome P-450 2 of phenobarbital treated rabbits, Biochem. Biophys. Res. Commun. 111: 926 (1983).
F. DeMatteis, A. H. Gibbs and T. R. Tephly, Inhibition of protohaem ferrolyase in experimental porphyria. Isolation and partial characterization of a modified porphyrin inhibitor, Biochem. J. 188: 145 (1980).
T. R. Tephly, A. H. Gibbs, G. Ingall and F. DeMatteis, Studies on the mechanism of experimental porphyria and ferrochelatase inhibition produced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine, J. Int. Biochem. 12: 993 (1980).
P. R. Ortiz de Montellano, H. S. Beilan and K. L. Kunze, N-methylprotoporphyrin IX: chemical synthesis and indentification as the green pigment produced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine treatment, Proc. Natl. Acad. Sci. USA 78: 1490 (1981).
T. R. Tephly, B. L. Coffman, G. Ingall, A. Zeit-Har, H. M. Goff, H. D. Tabba and K. M. Smith, Identification of N-methylprotoporphyrin IX in livers of untreated mice and mice treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC): Source of the methyl group, Arch. Biochem. Biophys. 212: 120 (1981).
F. DeMatteis, A. H. Gibbs, P. B. Farmer and J. H. Lamb, Liver production of N-alkylated porphyrins caused in mice by treatment with substituted dihydropyridines: evidence that the alkyl group on the pyrrole nitrogen originates from the drug, FEBS Letters, 129: 328 (1981).
B. L. Coffman, G. Ingall and T. R. Tephly, The formation of N-alkylprotoporphyrin IX and destruction cytochrome P-450 in the liver of rats after treatment with 3,5-diethoxycarbonyl-1,4dihydrocollidine and its 4-ethyl analogue, Arch. Biochem. Biophys. 218: 220 (1982).
F. DeMatteis and B. E. Prior, Experimental hepatic porphyria caused by feeding 3,5-diethoxycarbonyl-1,4-dihydro-2,46,-trimethylpyridine, Biochem. J. 83: 1 (1962).
T. Omura and R. Sato, The carbon monoxide-binding pigment of liver microsomes II solubilization, purification, and properties, J. Biol. Chem. 239: 2370 (1964).
Y. Imai, A. Ito and R. Sato, Evidence for biochemically different types of vesicles in the hepatic microsomal fraction, J. Biochem. 60: 417 (1966).
R. A. Prough, M. D. Burke and R. T. Mayer, Direct fluorometric methods for measuring mixed function oxidase activity, Methods Enzymol. 52: 399 (1978).
J. Baron and T. R. Tephly, Effect of 3-amino-1,2,4-triazole on the induction of rat hepatic microsomal oxidases, cytochrome P-450 and NADPH-cytochrome c reductase by phenobarbital, Mol. Pharmacol. 5: 10 (1969).
K. W. Bock, B. Burchell, G. J. Dutton, 0. Hanninen, G. J. Mulder, I. S. Owens, G. Siest and T. R. Tephly, UDP-glucuronyltransferase activities. Guidelines for consistent interim terminology and assay conditions. Biochem. Pharmacol. 32: 953 (1983).
D. J. Waxman, A. Ko and C. Walsh, Regioselectivity and stereoselectivity of androgen hydroxylations catalysed by cytochrome P-450 isozymes purified from phenobarbital-induced rat Liver, J. Biol. Chem. 258: 11937 (1983).
M. M. Bradford, A rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of protein dye binding, Analyt. Biochem. 72: 248 (1976).
K. E. McMartin, G. Martin-Amat, A. B. Makar and T. R. Tephly, Methanol poisoning. V. Role of formate metabolism in the monkey, J. Pharmacol. Exp. Thor. 201: 564 (1977).
K. A. Black, V. Virayotha and T. R. Tephly, Reductio?4of hepatic tetrahydrofolatg4and inhibition of exhalation of CO2 formed from [dimethylamino- CI-aminopyrine in nitrous oxide-treated rats, Hepatology 4: 871 (1984).
J. T. Eells, A. B. Makar, P. E. Noker and T. R. Tephly, Methanol poisoning and formate oxidation in nitrous oxide treated rats, J. Pharmacol. Exp. Ther. 217: 57 (1981).
K. E. McMartin, V. Virayotha and T. R. Tephly, High-pressure liquid chromatography separation and determination of rat liver folates, Arch. Biochem. Biophys. 209: 127 (1981).
L. S. Kaminsky, M. J. Fasco and F. P. Guengerich, Production and application of antibodies to rat liver cytochrome P-450, Methods Enzymol. 74: 262 (1981).
F. P. Guengerich, P. Wang and N. K. Davidson, Estimation of isozymes of microsomal cytochrome P-450 in rats, rabbits and humans using immunochemical staining coupled with sodium dodecyl sulfatepolyacrylamide gel electrophoresis, Biochemistry 21: 1698 (1982).
D. Larrey, L. M. Distlerath, G. A. Dannan, G. R. Wilkinson and F. P. Guengerich, F.P. Purification and characterization of the rat liver microsomal cytochrome P-450 involved in the 4-hydroxytion of debrisoquine, a prototype for genetic variation in oxidative drug metabolism, Biochemistry 23: 2787 (1984).
O. Augusto, H. S. Beilan and P. R. Ortiz de Montellano, The catalytic mechanism of cytochrome P-450. Spin-trapping evidence for one-electron substrate oxidation, J. Biol. Chem. 257: 11288 (1982).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1986 Plenum Press, New York
About this chapter
Cite this chapter
Tephly, T.R., Black, K.A., Green, M.D., Coffman, B.L., Dannan, G.A., Guengerich, F.P. (1986). Effect of a Suicide Substrate on the Metabolism of Steroids and Xenobiotics and on Cytochrome P-450 Apoproteins. In: Kocsis, J.J., Jollow, D.J., Witmer, C.M., Nelson, J.O., Snyder, R. (eds) Biological Reactive Intermediates III. Advances in Experimental Medicine and Biology, vol 197. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5134-4_21
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5134-4_21
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5136-8
Online ISBN: 978-1-4684-5134-4
eBook Packages: Springer Book Archive