Transsulfuration Is a Significant Source of Sulfur for Glutathione Production in Human Mammary Epithelial Cells

Figure 1

The transsulfuration pathway connects methionine and glutathione biosynthesis. In the methionine cycle, methionine forms S-adenosylmethionine which serves as a methyl donor, generating S-adenosyl homocysteine. This is converted to homocysteine, which is subsequently converted back into methionine. Homocysteine has an alternative fate, however. It can be used to produce cystathionine, which is further converted to cysteine. This latter conversion is catalyzed by gamma-cystathionase and inhibited by propargylglycine. Cysteine can then feed glutathione biosynthesis through production of gamma-glutamylcysteine. This step is catalyzed by gamma-glutamylcysteine synthase and inhibited by buthionine sulfoximine.