Extracellular glutathione is a source of cysteine for cells that express gamma-glutamyl transpeptidase

Biochemistry. 1993 Jun 22;32(24):6302-6. doi: 10.1021/bi00075a026.


We show that gamma-glutamyl transpeptidase (GGT) is a glutathionase that enables cells to use extracellular glutathione as a source of cysteine. We transfected NIH/3T3 mouse fibroblasts with a plasmid containing cDNA for human GGT, and obtained stably transformed cell lines that expressed GGT in its proper orientation on the outer surface of the cell. NIH/3T3 fibroblasts require cysteine for growth and are unable to use extracellular glutathione as a source of cysteine. We demonstrate GGT-positive fibroblasts are able to grow in cysteine-free medium supplemented with glutathione. Cysteine derived from the cleavage of extracellular glutathione can be used to maintain intracellular levels of glutathione. GGT-positive NIH/3T3 cells were able to replenish intracellular glutathione when incubated in cysteine-free medium containing glutathione. GGT-negative cells could not. Therefore, GGT is a glutathionase that provides the cell with access to a secondary source of cysteine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Culture Media
  • Cysteine / metabolism*
  • DNA
  • Glutathione / metabolism*
  • Humans
  • Kidney / enzymology
  • Mice
  • Rats
  • gamma-Glutamyltransferase / biosynthesis*
  • gamma-Glutamyltransferase / genetics


  • Culture Media
  • DNA
  • gamma-Glutamyltransferase
  • Glutathione
  • Cysteine