Enzyme induction

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An enzyme induction describes the induction of the gene expression of an enzyme . An enzyme induction increases the concentration of an enzyme. In addition to enzyme induction, enzyme activation leads to an increase in enzyme activity . A substance that causes induction is called an inducer in biochemistry . A repression of gene expression as the opposite of enzyme induction is achieved by repressors , and enzyme inhibition can also take place.

Enzyme induction in medicine

The effect of induction is used in the breakdown of drugs and in the event of poisoning in order to biotransform toxic substances as quickly as possible . One example is the induction of the enzyme cytochrome P450 by St. John's wort . Cytochrome P450 is responsible for the metabolism ( metabolism ) of numerous medicinal substances. Active ingredients such as Marcumar , HAART drugs, antibiotics or certain oral contraceptives can be broken down more quickly by the human organism. It is therefore possible that e.g. B. when taking St. John's wort at the same time, these medicinal substances cannot work sufficiently for the desired period of time (pill = 24 hours). Far more devastating are the possible consequences of the combined intake of an enzyme inducer and certain immunosuppressants. These are often prescribed after an organ transplant and prevent implanted organs from being rejected.

Enzyme inhibitors can be used to prevent drugs from being broken down too quickly. This saves on the use of drugs such. B. in the case of very expensive active ingredients or active ingredients that have more pronounced side effects in higher doses.

literature

Reviews on enzyme induction

  • JH Lin: CYP induction-mediated drug interactions: in vitro assessment and clinical implications. In: Pharm Res . , Volume 23, No. 6, June 2006, pp. 1089-1116. Review.
  • M. Dickins: Induction of cytochromes P450. In: Curr Top Med Chem . , Volume 4, No. 16, 2004, pp. 1745-1766.
  • MJ Gómez-Lechón, MT Donato, JV Castell, R. Jover: Human hepatocytes in primary culture: the choice to investigate drug metabolism in man. In: Curr. Drug metab. , Volume 5, No. 5, October 2004, pp. 443-462.
  • C. Handschin, UA Meyer: Induction of drug metabolism: the role of nuclear receptors. In: Pharmacol Rev . , Vol. 55, No. 4, December 2003, pp. 649-673.
  • EM Williamson: Drug interactions between herbal and prescription medicines. In: Drug Saf . , Vol. 26, No. 15, 2003, pp. 1075-1092.
  • AH Conney: Induction of drug-metabolizing enzymes: a path to the discovery of multiple cytochromes P450. In: Annu Rev Pharmacol Toxicol . , Volume 43, 2003, pp. 1-30.

Reviews on the mechanism of enzyme inhibition

  • Y. Masubuchi, T. Horie: Toxicological significance of mechanism-based inactivation of cytochrome p450 enzymes by drugs. In: Crit Rev Toxicol . , Volume 37, No. 5, June 2007, pp. 389-412.
  • S. Ferrari: Protein kinases controlling the onset of mitosis. In: Cell. Mol. Life Sci. , Vol. 63, Nos. 7-8, April 2006, pp. 781-795.
  • S. Zhou, Chan S. Yung, Goh B. Cher, E. Chan, W. Duan, M. Huang, HL McLeod: Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. In: Clin Pharmacokinet . , Vol. 44, No. 3, 2005, pp. 279-304.

Textbook

  • Hans Marquardt, Siegfried G. Schäfer (Eds.): Textbook of Toxicology 2nd Edition, Wissenschaftliche Verlagsgesellschaft Stuttgart, 2004.

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