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Synthesesteigerung und Abbauhemmung bei der Vermehrung der mikrosomalen Cytochrome P-450 und b-5 durch Phenobarbital

Increased synthesis and inhibited breakdown during the increase of microsomal cytochromes P-450 and b-5 after phenobarbital

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Summary

Heme moieties of microsomal rat liver cytochromes P-450 and b-5 were labeled with.14C-Aminolevulini cacid. The half life of the b-5 heme radioactivity was found to be 45 hrs, that of the P-450 heme radioactivity was 22 hrs.

Treatment of fed rats with Phenobarbital (80 mg/kg i.p. and 1‰ PB in the drinking water) for 48 hrs increased the concentration of cytochrome P-450 up to 200%, only by induced synthesis. In starved rats treated with Phenobarbital, P-450 concentration was increased up to 400%, by both induced synthesis and inhibition of breakdown.

Microsomal P-450 cytochrome was determined in rat liver homogenate and in suspensions of rat liver microsomes. The amount of P-450 obtained in the isolated microsomal fraction was compared with the P-450 content in the liver homogenate. Since P-450 is a microsomal hemoprotein this relation can be correlated with the microsomal protein, in order to to calculate the real content of microsomal protein in the liver homogenate. It was found to be 65 mg/g of liver, demonstrating, that 31% of the 209 mg of total protein/g of liver consists if microsomal protein.

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Literatur

  • Arias, I. M., Doyle, D., Schimke, R. T.: Studies on the synthesis and degradation of proteins of the endoplasmic reticulum of rat liver. J. biol. Chem.244, 3303 (1968).

    Google Scholar 

  • Aurapara, A.: Effect of protein depletion on the transaminating activation of some rat organs. J. biol. Chem.200, 537 (1953).

    Google Scholar 

  • Baron, J., Tephly, T. R.: Effect of 3-amino-1,2,4-triazole on the stimulation of hepatic microsomal heme synthesis and induction of hepatic microsomal oxidases produced by phenobarbital. Molec. Pharmacol.5, 10 (1969).

    Google Scholar 

  • DeMatteis, F.: Disturbances of liver porphyrin metabolism caused by drugs. Pharmacol. Rev.19, 523 (1967).

    Google Scholar 

  • Falk, J. E.: Porphyrins and metalloporphyrins, Chapter 14, p. 189, B.B.A. Library, Vol. 2. Amsterdam-London-New York: Elsevier Publ. Comp. 1964.

    Google Scholar 

  • Garner, R. C., McLean, A. E.: Separation of haem incorporation from protein synthesis in liver microsomes. Biochem. biophys. Res. Commun.37, 883 (1969).

    Google Scholar 

  • Greim, H., Remmer, H.: Veränderung des Eisenstoffwechsels in der Leber unter Phenobarbitalbehandlung. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.251, 110 (1965).

    Google Scholar 

  • —, Schenkman, J. B., Klotzbücher, M., Remmer, H.: The influence of phenobarbital on the turnover of hepatic microsomal cytochrome b-5 and cytochrome P-450. Biochim. biophys. Acta (Amst.)201, 20 (1970).

    Google Scholar 

  • —, Seifert, J.: Die Wirkung von Phenobarbital auf das proteosynthetische System der Rattenleber. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.260, 123 (1968).

    Google Scholar 

  • Jick, H., Shuster, L.: The turnover of microsomal reduced nicotinamide adenine dinucleotide phosphate-cytochrome C-reductase in the livers of mice treated with phenobarbital. J. biol. Chem.241, 5366 (1966).

    Google Scholar 

  • Kuriyama, W., Omura, T., Siekevitz, P., Pallade, G. E.: Effects of phenobarbital on the synthesis and degradation of the protein components of rat liver microsomal membranes. J. biol. Chem.244, 2017 (1968).

    Google Scholar 

  • Layne, E.: Spectrophotometric and turbidimetric methods for measuring proteins. Methods in Enzymology, Vol. III, p. 447. New York-London: Academic Press 1957.

    Google Scholar 

  • Levin, W., Kuntzman, R.: Biphasic decrease of radioactive hemoprotein from liver microsomal CO-binding particles. J. biol. Chem.244, 3671 (1968).

    Google Scholar 

  • Levitt, M., Shacter, A., Zipursky, A., Israels, L. G.: The nonerythropoetic component of early labeled bilirubin. J. clin. Invest.47, 1881 (1968).

    Google Scholar 

  • Mayer, G., Ullrich, V., Staudinger, H. J.: Possible involvement of cytochrome b-5 inl-kynurenine-3-hydroxylase of rat liver mitochondria. Hoppe-Seylers Z. physiol. Chem.349, 459 (1968).

    Google Scholar 

  • Newsholme, E. A., Greves, W.: Control of glycolysis and gluconeogenesis in liver and kidney cortex. Vitam. and Horm.25, 1 (1967).

    Google Scholar 

  • Omura, T., Sato, R.: The carbon monoxide binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J. biol. Chem.239, 2370 (1964a).

    Google Scholar 

  • ——: The carbon monoxide binding pigment of rat liver microsomes. II. Solubilisation, purification, properties. J. biol. Chem.239, 2379 (1964b).

    Google Scholar 

  • Paul, K. G., Theorell, H., Akeson, A.: The molar light absorption of pyridine ferroprotoporphyrine (pyridin haemochromogen). Acta chem. scand.7, 1284 (1953).

    Google Scholar 

  • Remmer, H., Greim, H.: Drug tolerance by increased drug metabolism. In: Radioactive isotopes, ed. by Glasson and Waser. London: Wiley Ltd. 1969.

    Google Scholar 

  • —, Siegert, M.: Kumulation und Elimination von Phenobarbital. Naunyn-Schmie-debergs Arch. exp. Path. Pharmak.243, 479 (1962).

    Google Scholar 

  • Rosen, F., Roberts, N. R., Nicols, C. A.: Glucocorticoids and transaminase activity. I. Increased activity of glutamic pyruvic transaminase in four conditions associated with gluconeogenesis. J. biol. Chem.234, 476 (1959).

    Google Scholar 

  • Schimke, R. T., Ganschow, R., Doyle, D., Arias, J. M.: Regulation of protein turnover in mammalian tissues. Fed. Proc.27, 1223 (1968).

    Google Scholar 

  • Schmidt-Volkmar, W.: Der Einfluß von Hunger und Phenobarbitalbehandlung auf die Aktivität der hydroxylierenden mikrosomalen Enzyme der Ratte. Inaugural-Dissertation, Tübingen 1966.

  • Shuster, L., Jick, H.: The turnover of microsomal protein in the livers of phenobarbital-treated mice. J. biol. Chem.241, 5361 (1966).

    Google Scholar 

  • Snyder, A. L., Schmid, R.: The conversion of hematin to bile pigment in the rat. J. Lab. clin. Invest.65, 817 (1965).

    Google Scholar 

  • Start, C., Newsholme, E. A.: The effects of starvation and alloxan-diabetes on the contents of citrate and other metabolic intermediates in rat liver. Biochem. J.107, 411 (1968).

    Google Scholar 

  • Tenhunen, R., Marver, H. S., Schmid, R.: The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc. nat. Acad. Sci. (Wash.)61, 748 (1969).

    Google Scholar 

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Greim, H. Synthesesteigerung und Abbauhemmung bei der Vermehrung der mikrosomalen Cytochrome P-450 und b-5 durch Phenobarbital. Naunyn-Schmiedebergs Arch. Pharmak. 266, 261–275 (1970). https://doi.org/10.1007/BF00997287

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