Title:A Simple Identification of Novel Carbonyl Reducing Enzymes in the Metabolism of the Tobacco Specific Carcinogen NNK
VOLUME: 6 ISSUE: 3
Author(s):Lucie Skarydova, Michaela Zverinova, Hana Stambergova and Vladimir Wsol
Affiliation:Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 50005 Hradec Kralove, Czech Republic.
Keywords:Activity, carbonyl, enzymes, HPLC-UV, NNK, NNAL, SDR, reducing.
Abstract:Tobacco smoking is the most widely known cause of human cancer-related death worldwide. NNK is one of
the proved human carcinogens contributing to the development of several types of cancer. The carcinogenic effect of
NNK depends on the metabolic pathway. Reduction of NNK by carbonyl reducing enzymes leads to the formation of
NNAL. This pathway is generally regarded as detoxification pathway although the conditions and circumstances are quite
complicated - the process depends on a formed enantiomer of NNAL.
In this study a novel method for the determination of the metabolite NNAL was developed. This makes it possible to find
and characterize carbonyl reducing enzymes that are involved in NNK metabolism. This simple HPLC method uses
conventional HPLC instrumentation and is designed mainly for biochemical laboratories. A new microsomal carbonyl
reducing enzyme participating in the metabolism of NNK in vitro has been described. Its activity was compared with
other carbonyl reducing enzymes taking part in the biotransformation of NNK.
