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Adv Exp Med Biol. 2018;1032:37-53. doi: 10.1007/978-3-319-98788-0_3.

Glutathione and Transsulfuration in Alcohol-Associated Tissue Injury and Carcinogenesis.

Author information

1
Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA. ying.chen@yale.edu.
2
Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA.
3
College of Environment and Resource, Shanxi University, Taiyuan, Shanxi, China.
4
Department of Social Medicine, Saga University School of Medicine, Saga, Japan.
5
Department of Clinical Pharmacy, University of Colorado School of Pharmacy, Aurora, CO, USA.

Abstract

Glutathione (GSH) is the most abundant non-protein thiol, attaining cellular concentrations in the millimolar range. GSH functions to protect cells against endogenous and exogenous electrophiles. In addition, GSH serves as a cofactor for the GSH peroxidase family of enzymes which metabolize H2O2 as well as lipid peroxides. Through the action of glutathione S-transferase family of enzymes, GSH is conjugated to a variety of electrophilic endogenous compounds and exogenous chemicals, and thereby facilitates their efficient and safe elimination. Through the transsulfuration pathway, GSH biosynthesis is metabolically linked with cellular methylation, which is pivotal for epigenetic gene regulation. Accumulating evidence suggests that the underlying mechanisms of alcohol-associated tissue injury and carcinogenesis involve: (i) generation of the electrophilic metabolite acetaldehyde, (ii) induction of CYP2E1 leading to the formation of reactive oxygen species and pro-carcinogen activation, and (iii) nutritional deficiencies, such as methyl groups, resulting in enhanced susceptibility to cancer development. In this context, clinical and experimental investigations suggest an intimate involvement of GSH and related enzymes in the development of alcohol-induced pathological conditions. The aim of this review is to provide an overview of the GSH biosynthesis, cellular transsulfuration/transmethylation pathways, and their implications in the pathogenesis and treatment of alcohol-related disease and cancer.

KEYWORDS:

Alcoholic; Cancer; Glutathione; Methylation; Oxidative stress; Transsulfuration

PMID:
30362089
DOI:
10.1007/978-3-319-98788-0_3
[Indexed for MEDLINE]

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