Daotong Li, Pengpu Wang, Yanbing Liu, Xiaosong Hu, Fang Chen1. 1. College of Food Science and Nutritional Engineering, China Agricultural University, No.17, Qinghua East Road, Haidian District, Beijing 100083, China. chenfangch@sina.com.
Abstract
BACKGROUND: Acrylamide (AA), a known neurotoxin, has been considered to be a probable human carcinogen. The discovery of AA in many common foods in 2002 has caused worldwide attention and led to numerous research efforts on the metabolism of AA. METHODS: By collecting research literatures related to metabolism of AA, the present review not only summarized the major metabolic pathways and enzymes of AA, but also compared the interindividual and the interspecies differences of AA metabolism among humans, rats and mice. Moreover, the application of the metabolites as biomarkers for the AA exposure assessment in human population was also discussed. RESULTS: The interindividual differences of AA metabolism may be attributed to the activity and/or genetic polymorphisms of metabolic enzymes in individuals with different gender, age, smoking and alcohol status. Moreover, the metabolism of AA in humans may be more prone to the phase II conjugation with glutathione (GSH) than the phase I conversion of AA to glycidamide (GA) when compared with rats and mice. Both the hemoglobin (Hb) adducts and urinary mercapturic acid (MA) metabolites have been successfully used as biomarkers for the risk assessment of AA and new metabolic biomarkers are being developed. CONCLUSION: The genotoxic risk from AA may be determined by the balance between the phase I P450 2E1 (CYP2E1)-dependent toxification pathway to form genotoxic GA and the phase II GSH-conjugated detoxification pathway to form MA metabolite. Understanding the metabolism of AA in the body is helpful for developing effective intervention strategies to mitigate its toxicity.
BACKGROUND:Acrylamide (AA), a known neurotoxin, has been considered to be a probable human carcinogen. The discovery of AA in many common foods in 2002 has caused worldwide attention and led to numerous research efforts on the metabolism of AA. METHODS: By collecting research literatures related to metabolism of AA, the present review not only summarized the major metabolic pathways and enzymes of AA, but also compared the interindividual and the interspecies differences of AA metabolism among humans, rats and mice. Moreover, the application of the metabolites as biomarkers for the AA exposure assessment in human population was also discussed. RESULTS: The interindividual differences of AA metabolism may be attributed to the activity and/or genetic polymorphisms of metabolic enzymes in individuals with different gender, age, smoking and alcohol status. Moreover, the metabolism of AA in humans may be more prone to the phase II conjugation with glutathione (GSH) than the phase I conversion of AA to glycidamide (GA) when compared with rats and mice. Both the hemoglobin (Hb) adducts and urinary mercapturic acid (MA) metabolites have been successfully used as biomarkers for the risk assessment of AA and new metabolic biomarkers are being developed. CONCLUSION: The genotoxic risk from AA may be determined by the balance between the phase I P450 2E1 (CYP2E1)-dependent toxification pathway to form genotoxic GA and the phase II GSH-conjugated detoxification pathway to form MA metabolite. Understanding the metabolism of AA in the body is helpful for developing effective intervention strategies to mitigate its toxicity.
Authors: Clara Amalie Gade Timmermann; Signe Sonne Mølck; Manik Kadawathagedara; Anne Ahrendt Bjerregaard; Margareta Törnqvist; Anne Lise Brantsæter; Marie Pedersen Journal: Toxics Date: 2021-06-30