Modern Biochemical Aspects of Xenobiotic Detoxification System. Literature Review

Foreign chemicals that are usually considered as "xenobiotics" are commonly used environmental factors, which can have a negative impact on the body. It is proved that most xenobiotics do not have a direct biological effect due to their previous biotransformation (metabolism). The process of biotransformation is based mainly on the xenobiotics detoxification, which is why it is considered to be one of the protective and adaptive mechanisms. Violation of biochemical mechanisms of xenobiotics detoxification is one of the reasons for the imbalance of homeostasis and the development of pathological processes. The process of xenobiotics detoxification consists of three phases: activation, neutralization and excretion from the body. The combined action of the first two phases usually leads to increased hydrophilicity and decreased activity and toxicity of xenobiotics. The most important link in the first phase of xenobiotics detoxification is the monooxygenase system, which is localized in the membranes of the endoplasmic reticulum and is represented by cytochromes P450 and b5, NADH and NADH reductases. The first phase is based primarily on oxidative transformations involving enzymes of cytochrome P-450 families, flavin-dependent monooxygenase, alcohol dehydrogenase, aldehyde dehydrogenase, prostaglandin synthase. In this phase there may also occur hydrolysis reactions with the participation of arylstearase, carboxyletherase. Increasing the xenobiotics polarity decreases their lipophilicity and greatly enhances the possibility of excretion. The second phase of xenobiotics detoxification, the conjugation phase, is also aimed at increasing hydrophilicity and reducing the toxicity of the xenobiotics due to the action of mainly enzymes of transferases class: glutathione transferase, UDP-glucuronyltransferase, arylamine-N-acetyltransferase, sulfotransferase, acetyltransferase, methyltransferase. The effectiveness of the xenobiotics detoxification system is due to the individual genetic features of the organism, which determine the differential individual's sensitivity to environmental factors in the form of compensatory-adaptive reactions. The third phase of xenobiotics detoxification ensures the detoxification products excretion from the body through the lungs, kidneys, gastrointestinal tract. Xenobiotics with significant hydrophobicity and molecular weight are excreted with bile. There are various mechanisms for the conjugates elimination from the body: through the ATP-dependent ion pump, with the participation of highly specific transporters of organic anions and dinitrophenol conjugates of glutathione, P-glycoprotein and a number of proteins that can cause multiple resistance to xenobiotics. The above-mentioned analytical review of literature on general ideas about the process of xenobiotics detoxification in the human body and animals does not claim to be its complete coverage. The theoretical generalizations, which are given above and scientific approaches should be taken into account when studying the biochemical mechanisms of neutralization xenobiotics processes violations and the development of means for their correction.