Several classes of enzyme are involved in the detoxification of xenobiotics in the human body. Investigations of enzyme systems are of interest in occupational medicine, where there is exposure to xenobiotics, and also in persons with unexplained reactions to environmental toxins.
GST: Glutathione S transferases (GSTs) are multifunctional enzymes which play an important role in cell detoxification. Several classes of GST (GSTA, GST-T, GST-M, GST-P , GST-K, GST-Z) have been identified. GSTs protect the cells by conjugating toxic substances with glutathione. Glutathione conjugations are generally less toxic and more water-soluble than the original substances, and thus more easily excreted. However, during the detoxification process there are also several reactive interim stages which may have a toxic effect. Endogenous substrates of GSTs include not only various by-products of oxidative metabolism but also many drugs and xenobiotics such as organic halides, alkenes, epoxides and benzapyrenes.
NAT2: The N-acetyltransferases NAT1 and NAT2 are the catalysts for the detoxification of xenobiotics through the acetylisation of various functional groups within the human body. NAT2 substrates include not only aromatic amines (e.g. naphtylamine or benzinidine), but also drugs (e.g. isoniazide, sulfonamides and hydralazine). Various polymorphisms in the NAT2 gene create a greater or lesser acetylating capacity. Approximately 70% of Caucasians are "slow acetylators".
CYP1A1: Cytochrome P450-1A1 (CYP1A1) belongs to the group of Phase I enzymes and initiates the breakdown of environmental toxins, such as polyaromatic hydrocarbons (PAHs), and various xenobiotics. In approximately 10% of Caucasians enzyme activity is more easily induced due to genetic polymorphisms.
CYP1A2: CYP1A2 plays a part in the oxidative metabolism of a series of environmental toxins such as essential and heterocyclic amines and various drugs. The CYP1A2 enzyme system can be induced by several substances (e.g. cigarette smoke). Numerous variants associated with altered enzyme activity are known of in the CYP1A2 gene. It has not so far been possible to clarify the clinical relevance of these genetic variants in vivo; for this reason, investigation of the gene is not currently a part of the routine diagnostic process and will only be carried out, following consultation, if there are specific indications.
Xenobiotic detoxification within the body usually proceeds in several steps involving different enzyme systems. In many cases, the entire breakdown process with all the enzyme systems involved has not yet been described in detail. For this reason, analysis of the listed genes only provides limited information about the patient’s capacity for detoxification.
