Gamma-Glutamyl Transpeptidase (GGTP/GGT/γGT/GT)

EC 2.3.2.2

Gamma-Glutamyl Transpeptidase (GGT) is also known as Gamma-Glutamyl Transferase as well as by other names. GGT catalyzes the transfer of a gamma-glutamyl moiety to a wide variety of amino (and non-amino) acceptors¹. A simple example is the transfer of the γ-glutamyl moiety to the acceptor alanine:

Not only can GGT transfer the glutamyl moiety to many different acceptors, various γ-amino derivatives of glutamine can also be utilized as donors. A common method of measuring GGT is to use a chromogenic substrate such as γ-glutamyl-p-nitroanilide:

When GGT catalyzes the transfer of the γ-glutamyl moiety to an acceptor (usually glycylglycine), p-nitroaniline is released which can easily be measured by its absorbance at 415 nm.

Although the most abundant source of GGT is the kidney, and serum GGT is often elevated due to various kidney conditions, clinically GGT is predominantly a marker of liver pathologies². It is an especially useful marker of obstructive liver diseases such as biliary obstruction, cholangitis and cholecystitis as compared to ALP, ALT or AST³. Another interesting aspect of elevated serum GGT is that unlike most enzyme markers, in at least some circumstances the elevation of serum GGT is not due to a loss of enzyme activity, but rather due to an induction of it⁴. Serum GGT has also been found to be useful in assessing and following liver damage due to alcoholism⁵ and is a known risk predictor for the development of hepatoma and other cancers^6,7,8. It has also been used to predict treatment response in patients with hepatitis C, with a high pre-treatment serum level of GGT usually predicting a poor response to treatment^9,10. It has also been reported that GGT is an independent risk factor for developing type 2 diabetes¹¹. Thus GGT is a remarkably useful and versatile marker.

 

REFERENCES

1. 1. Tate, S.S. and Meister, A. Glutathione and Related γ-Glutamyl Compounds: Biosynthesis and Utilization. Annual Review of Biochemistry, 45, 559-604.
2. 2. Burtis, C.A., Ashwood, E.R. and Bruns, E.R. Tietz Textbook of Clinical Chemistry, W.B. Saunders Company, 2006.
3. 3. Lum, G. and Gambino, S.R. Serum Gamma-Glutamyl Transpeptidase Activity as an Indicator of Disease of Liver, Pancreas or Bone. Clinical Chemistry, 18, 358-362, 1972.
4. 4. Teschke, R., et. al. Hepatic Gamma-Glutamyltransferase Activity in Alcoholic Fatty Liver: Comparison with other Liver Enzymes in Man and Rats. Gut, 24, 625-630,1983.
5. 5. Kaur, I. and Sidhu, D.S. GGT Activity in Patients Suffering from Alcoholic Liver Disease in Relation to Duration, Quantity and Type of Alcoholic Beverage Consumed. Environment and Ecology, 16, 709-712, 1998.
6. 6. Strasak, A.M., et. al. Prospective Study of the Association of Gamma- Glutamyltransferase with Cancer Incidence in Women. International Journal of Cancer, 123, 1902-1906, 2008.
7. 7. Strasak, A.M., et. al. Association of Gamma-Glutamyltransferase and Risk of Cancer Incidence in Men: A Prospective Study. Cancer Research, 68, 3970-3977, 2008.
8. 8. Corti, A., et. al. Gamma-Glutamyltransferase of Cancer Cells at the Crossroads of Tumor Progression, Drug Resistance and Drug Targeting. Anticancer Research, 30, 1169-1180, 2010.
9. 9. Villela-Nogueira, C.A., et. al. Gamma-Glutamyltransferase (GGT) as an Independent Predictive Factor of Sustained Virologic Response in Patients with Hepatitis C Treated with Interferon-Alpha and Ribavirin. Journal of Clinical Gastroenterology, 39, 728-730, 2005.
10. 10. Paolicchi, A., et. al. Gamma-Glutamyltransferase in Fine Needle Biopsies of Subjects with Chronic Hepatitis C. Journal of Viral Hepatology, 12, 269-273, 2005.
11. 11. Perry, I.J., et. al. Prospective Study of Serum Gamma-Glutamyltransferase and risk of NIDDM. Diabetes Care, 21, 732-737, 1998.