Phase Two Detoxification

# What is phase 2 detoxification There are various mechanisms in the body for detoxification or the breakdown of harmful substances. The detoxification function in the body takes place in 3 phases. The organism makes use of a series of highly specific enzymes. Organs such as the liver or kidneys, which are particularly intensively involved in detoxification, have the highest enzyme density. Phase 1 detoxification: In this phase, chemical compounds are converted into a more easily degradable form. Foreign substances such as medicines, plasticizers, solvents and pesticides are broken down by enzymes and prepared for detoxification phase 2. Phase 2 detoxification: In this phase, the metabolites from phase 1 are further processed and converted into mainly water-soluble compounds so that they can be better excreted. As the resulting substances from phase 1 can sometimes even be more harmful than their original substance, a seamless transition between the phases of detoxification is important. Phase 2 focuses on special endogenous compounds such as glutathione, amino acids, sulphur or glycine, which are bound to the substance to be excreted. So-called conjugates (compounds) are formed, which are far less toxic than the original substances. Phase 2 detoxification therefore plays an important role in protecting our body from the harmful effects of pollutants. Genetic variants can influence the activity of phase 2 detoxification enzymes. For example, carriers of certain variations may have an increased tendency to accumulate toxins in the body or show a reduced detoxification capacity. Nutrients such as B vitamins, vitamin C, vitamin E, magnesium, zinc and antioxidants support the liver during detoxification. > ## The three detox phases summarized >Phase 1 Detoxification: Substances that must be excreted are converted into a more easily degradable form. > >Phase 2 detoxification: The metabolites from phase 1 are bound via the glutathione system and prepared for excretion. > >Phase 3 detoxification: Fat-soluble substances are excreted via the liver and bile and water-soluble substances via the kidneys. # What do genetics have to do with it? We are investigating five genes involved in phase 2 detoxification: In cells, the NQO1 gene carries the blueprint for the enzyme NQO1, which catalyzes chemoprotective, antioxidant and detoxifying reactions. For example, it is involved in the defense against oxidative stress as well as in the conversion of coenzyme Q10 and the conversion of vitamin K in the body. The enzyme NQO1 is also involved in the degradation of external toxins such as benzene and other groups of substances. Two common variants of the gene impair the enzyme activity of NQO1 and increase the risk of pollutant-related diseases. - Variant rs1800566 of the NQO1 gene: Genotypes A/A show no enzyme activity and a greatly increased risk of pollutant-related diseases. Genotype A/G shows weak enzyme activity and an increased risk of pollutant-related diseases. The G/G genotype shows normal enzyme activity. - Variant rs1131341 of the NQO1 gene: Genotypes A/A show no enzyme activity and a greatly increased risk of pollutant-related diseases. Genotype A/G shows weak enzyme activity and an increased risk of pollutant-related diseases. The G/G genotype shows normal enzyme activity. The GSTM1 gene carries the blueprint for the enzyme glutathione S-transferase M1 in the cells, which binds glutathione to substances that must be excreted. This results in increased water solubility and facilitates the excretion of endogenous and exogenous substances. The GSTM1 enzyme is primarily responsible for the detoxification of carcinogenic substances, drugs, toxins and by-products of oxidative stress. It is also involved in the detoxification of mold toxins, in particular aflatoxin B1. Around 50-78% of the population has an inactive copy of the gene. Those affected have an increased risk of mycotoxin-mediated diseases, especially lung diseases. - Variant rs366631 of the GSTM1 gene: Genotypes A/A show no enzyme activity and a greatly increased risk of pollutant-related diseases. Genotypes A/G and G/G show normal enzyme activity. The SOD2 gene (superoxide dismutase 2 gene) carries the blueprint for the enzyme SOD2 in the cells, which is responsible for the degradation of toxins and the elimination of highly reactive oxygen species in the cell. Variants of the gene are associated with diseases of the heart muscle (idiopathic cardiomyopathy/IDC), premature ageing, neurological diseases, increased risk of asthma and radical-related diseases. - Variant rs5746136 of the SOD2 gene: The genotypes T/T show no enzyme activity and a greatly increased risk of pollutant-related diseases. The C/T genotype shows weak enzyme activity and an increased risk of pollutant-related diseases. Genotype C/C shows normal enzyme activity. The COX2 gene (cyclooxygenase 2 gene) carries the blueprint for the enzyme COX-2 in the cells, which is primarily involved in inflammatory reactions in the body and is primarily formed in the event of injury, inflammation or new cell formation (sprouting). - Variant rs5277 of the COX2 gene: The G/G genotype shows a higher risk of liver dysfunction if larger quantities of bisphenol-A (BPA) are ingested. BPA is a component of some plastics. It is now ubiquitous in the environment and can be detected in the bodies of > 90 % of the population. Genotypes C/C and C/G show normal enzyme activity and no increased risk. The catalase gene (CAT gene) carries the blueprint for the enzyme catalase in the cells, which is involved in cellular detoxification. People who have a variant of the gene and older people show reduced enzyme activity. Together with an increased intake of bisphenol-A (BPA), the risk of liver dysfunction increases. - Variant rs769217 of the CAT gene: The T/T genotype shows no enzyme activity. With increased amounts of bisphenol-A (BPA), the risk of liver dysfunction is increased. The C/T genotype shows weak enzyme activity and a slightly increased risk. Genotype C/C shows normal enzyme activity and no increased risk.