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Mechanisms in Multi-drug Resistance:
ABC-transporters and detoxification enzymes in hepatocytes
SIGMA-ALDRICH
Mechanisms in Multi-Drug Resistance: ABCtransporters and detoxification enzymes in
hepatocytes
The cellular components responsible for the phenomenon of multi-drug resistance (MDR) in
the structural context of hepatocytes include intrinsic transmembrane proteins, generically
called drug efflux pumps, and the enzymes responsible for detoxification and
biotransformation of xenobiotics. The enzymes include the cytochrome P450s (CYPs) and
the phase II conjugation enzymes such as glutathione-S-transferase (GST). The major drug
efflux pumps are in the superfamily of ABC (ATP-binding-cassette)-transporters. Of these
ABC-ATPases, the major subfamilies are the MDR/TAPs and MRPs (multi-drug resistance
related proteins). The natural substrates are indicated for the drug efflux pumps.
References:
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Di, P.A., et al., Modulation by flavonoids of cell multidrug resistance mediated by Pglycoprotein and related ABC transporters. Cell. Mol. Life Sci., 59, 307-322 (2002).
Meier, P.J., and Stiger, B., Bile salt transporters. Annu. Rev. Physiol., 64, 635-661 (2002).