Glutathione S-transferases are a family of phase 2 detoxification enzymes that play an important role in the metabolism of endogenous and exogenous compounds. Compounds that can be metabolised by the GST enzyme family include carcinogens, environmental toxins and reactive oxygen species. The two major GST isoforms in humans are GSTT1 and GSTM1. The GSTM1 gene encoding for the GSTM1 enzyme is deficient in roughly 50% of the population (53% white, 40-60% Asians and 21% Africans) and the GSTT1 gene encoding for the GSTT1 enzyme is deficient in roughly 20% of the population (18% whites, 45-60% Asians and 22% Africans). Decreased phase 2 detoxification, through deletion of GST enzymes or an ineffectively working phase 2 system has been associated with an increased risk of coronary heart disease, asthma, breast cancer, colon cancer, bladder cancer, liver cancer, lung cancer, oesophageal cancer, leukaemia and prostate cancer.
Because of the importance of the phase 2 detoxification pathway on the removal of toxins, inefficiencies in the system can result in higher levels of potentially damaging chemicals in tissues that may increase oxidative stress and inflammation. Researchers are therefore interested in possible marker of inflammation and oxidation, or nutrient factors, that might be associated with the GST system. To these ends, researchers1 have recorded the genotype deletions of the GST enzymes in 383 non-smokers who were not taking anti-inflammatory drugs or vitamin supplements and then analysed their serum for known biomarkers of oxidative stress, inflammation and antioxidant nutrients. Serum vitamin C was significantly higher in subjects with one inactive copy of the GSTM1 gene compared to those with the fully active GSTM1 genotype. In addition, dual deletion of GSTM1 and GSTT1 was associated with increased serum iron and total and LDL cholesterol and lower malondialdehyde concentrations.
It is not clear why subject with an inactive copy of the GSTM1 gene had significantly higher levels of ascorbic acid in their serum. One possible explanation is that subjects with GSTM1 deletions have compensatory increases in reabsorption and absorption of vitamin C from the kidneys and the intestines, respectively. Another possibility is that the GSTO2 enzymes, which function as dehydroascorbate reductases, are unregulated and increase the recycling of the oxidised form of vitamin C back to its reduced form. Just how these genes may become unregulated in not known, but the process may involve epigenetic influences brought about by the deletion of the GSTM1 gene. Again, it is not understood why the dual deletion of the GSTM1 and GSTT1 gene would cause changes in LDL and total cholesterol, iron and malondialdehyde concentrations. However, these findings should be taken into consideration when reviewing further research.
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