To be excreted in urine, glutathione conjugates undergo several hydrolysis steps to form mercapturic acids which are readily excreted. The first step is the hydrolysis of a gamma-glutamyl residue from the conjugate catalysed by gamma-glutamyltransferases (GGTs). These are membrane-bound, heterodimeric enzymes composed of light and heavy peptide chains. Extracellular glutathione (GSH) or its conjugates can be hydrolysed to produce cysteinylglycine (CG, or CG conjugates) and free glutamate (L-Glu). Defects in GGT1 can cause glutathionuria (GLUTH; MIM:231950), an autosomal recessive disorder characterised by increased GSH concentration in the plasma and urine. Mutations that cause GLUTH can occur in both chains of the GGT1 dimer. R107H and R107Q in the heavy chain play a significant role in substrate binding rather than catalysis (Ikeda et al. 1993). S451A, S452A, D423A and D423E mutations in the light, catalytic chain of GGT1 completely or almost completely result in loss of function of the enzyme (Ikeda et al. 1995, Ikeda et al. 1995b).