ABSTRACT
The Glutathione transferases (GSTs) are promiscuous in their substrate acceptance and collectively they detoxify various xenobiotics or metabolic by-products that otherwise could be harmful. Genes encoding GSTs in variant forms can be chemically synthesized, and expressed enzyme proteins can be produced and inserted directly into cells or produced intracellularly from transfected DNA. Human GSTs have been shown to activate different thiopurine prodrugs to release 6-mercaptopurine, which serves as an antimetabolite interfering with nucleotide metabolism and nucleic acid biosynthesis. The plant GSTs have modest activity and GSTs optimized by methods of biochemistry and molecular genetics are in demand. Introduction of GST proteins into living cells via transfection from eukaryote expression vectors perturbs the composition of the proteome by mechanisms that appear unrelated to the catalytic activities of GSTs, which can be verified by treatments with incapacitated mutants. Networks of cellular signaling may be influenced by GSTs and studies of proteomes as well as transcriptomes can explore these phenomena in cells.
