A Simple Identification of Novel Carbonyl Reducing Enzymes in the Metabolism of the Tobacco Specific Carcinogen NNK

Lucie      Skarydova; Michaela      Zverinova; Hana      Stambergova; Vladimir      Wsol

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.

Keywords: Activity, carbonyl, enzymes, HPLC-UV, NNK, NNAL, SDR, reducing.