Gamma-Glutamyl Transferase (γ-GT) - an old dog with new tricks?

Gamma-Glutamyl Transferase (γGT) is a key transferase involved in the transpeptidation of functional gamma-glutamyl groups to various receptor moieties. It performs important roles in antioxidant defence mechanisms, particularly glutathione recycling, xenobiotic metabolism, but analogously may also have a pro-oxidant role. γGT is very sensitive for the diagnosis of liver injury, although it has poor specificity for particular aetiologies. It has been used to reflect temporal changes as a form of monitoring depending on aetiology. Given its cellular role in antioxidant function, it has been investigated as a surrogate biomarker of oxidative stress. It has also been found to be a predictor of mortality across a spectra of non-hepatic disease pathologies, from metabolic and cardiovascular risk to chronic kidney disease and neoplasia. Similarly, it also remains of interest to the insurance industry given an apparent ability to predict mortality, in addition to a historical interest from law enforcement as a marker of chronic alcohol ingestion. Here, we review some of the unique characteristics of this important enzyme, previously considered as a mere specific marker of liver dysfunction, but now with clear extra-hepatic implications and novel applications and utility.