γ-L-glutamyltaurine

The discovery of the dipeptide γ-glutamyltaurine (γ-GT; glutaurine, Litoralon) in the parathyroid in 1980 and later in the brain of mammals gave rise to studies on intrinsic and synthetic taurine peptides of this type. It was suggested that γ-glutamyltransferase (GGT; γ-glutamyl-transpeptidase) in the brain is responsible for the in vivo formation of this unusual dipeptide. γ-GT has been prepared by both synthetic and enzymatic methods. The chemical syntheses included the use of protecting groups and coupling methods. A wide spectrum of analytical and spectroscopic methods was used to confirm the structure of the synthetic compounds and to elucidate the position of the peptide bond. Enzymatic preparation of γ-GT from taurine takes advantage of the selective transpeptidation action of GGT on L-glutamine, glutathione, γ-glutamyl-p- nitroanilide or other glutamine donors. Although the functional roles of γ-GT in the brain are only poorly understood, many of its established CNS effects have been reported in the last 25 years. Its effect on emotional arousal and its anti-conflict potencies are synergistic with the anxiolytic drug diazepam. γ-GT exhibits anti-conflict potency, which is exerted by reducing aversion or phobia and/or the anxiety levels. γ-GT also acts as endogenous modulator in excitatory aminoacidergic neurotransmission. It is suggested that such acidic peptides through N-methyl-D-aspartic acid receptors could be part of the neurochemical substrate underlying self-stimulation of the medial pre-frontal cortex. Other γ-GT effects in neural systems include: effects on the monoamine concentration in the brain; effects on aggressive behavior in the cat; effects on thyroid hormones in the rat; amelioration of electroshock-induced amnesia; potent and long-lasting antiepileptic action (on intraamygdaloid injection); affect the glutamatergic system in schizophrenic disorders. Roles for γ-GT in non-neural systems have also been reported, e.g., effects on the metamorphosis of amphibians; on plasma rennin regulation; on radiation protection; on uric acid levels; on human antibody-dependent cell-mediated cytotoxicity (ADCC) and many more.