It can not be from the liver...................or it is?

GGT is found in cells of many organs, primarily liver, kidney and pancreas. It is present in highest concentrations in the kidney but the primary source of GGT in serum is generally considered to be the liver. Chronic alcohol intake results in increased GGT activity in the liver cells but the exact mechanism for increased serum GGT is not clear. In the past decade, GGT has been implicated in other disorders such as cardiovascular disease and conditions related to obesity such as diabetes and non-alcoholic liver disease. A recent review by the group from Pisa (Italy) "The Significance of Serum Gamma Glutamyltransferase in Cardiovascular Diseases" appeared in Clinical Chemisty and Laboratory Medicine (2004) 42(10):1085-1091 full article available on web at: http://www.sorta-biomedical.com/installazioni/pompella/allegati/pagine/89/2004_CCLM.pdf

GGT is present in the cell membranes of many tissues, including the kidneys, bile duct, pancreas, gallbladder, spleen, heart, brain, and seminal vesicles.

It is involved in the transfer of amino acids across the cellular membrane and leukotriene metabolism. It is also involved in glutathione metabolism by transferring the glutamyl moiety to a variety of acceptor molecules including water, certain L-amino acids, and peptides, leaving the cysteine product to preserve intracellular homeostasis of oxidative stress. This general reaction is:

(5-L-glutamyl)-peptide + an amino acid peptide + 5-L-glutamyl amino acid

Elevated serum GGT activity can be found in diseases of the liver, biliary system, and pancreas. In this respect, it is similar to alkaline phosphatase (ALP) in detecting disease of the biliary tract. Indeed, the two markers correlate well, though there is conflicting data about whether GGT has better sensitivity.In general, ALP is still the first test for biliary disease. The main value of GGT over ALP is in verifying that ALP elevations are, in fact, due to biliary disease; ALP can also be increased in certain bone diseases, but GGT is not.

Elevated levels of GGT may also be due to congestive heart failur. Slight elevations in serum GGT levels are also seen in other cardiovascular disease, in particular, GGT accumulates in atherosclerotic plaques. More recently, slightly elevated serum GGT has also been found to correlate with cardiovascular diseases and is under active investigation as a cardiovascular risk marker.

GGT-containing protein aggregates circulate in the blood in certain pathologies such as metabolic syndrome (high body mass index associated with type 2 diabetes).

So, there is ample agreement that the source of serum GGT is liver. The real question arises here;

Studies show that GGT is localized on the extra cellular surface of the cholangiocytes facing the bile duct lumen and also in the canalicular region of the neighboring hepatocytes in the liver. Assuming the physiological uninterrupted bile flow(as in alcoholic consumption), GGT from these cells should flow along the bile current and should end in the intestine. Where it will be degraded (GGT is an protein enzyme). In that case only two possibilities may be envisioned 1) GGT maybe highly resistant to degradation in the GIT, or due to some mechanism it may flow through the sinusoidal side and reaches in the serum.

Any other idea or suggestion?

I think you're right. As far as I know GTT half-life is relatively long and is about 10 days. I'd recommend the following data sources:

McPherson: Henry's Clinical Diagnosis and Management by Laboratory Methods. 22nd ed

Atta, excellent question. In biliary disorders, the literature suggests a cholangiocyte origin of increased serum GGT. However, in non-biliary chronic alcohol liver disorder, the origini of increased serum GGT is more likely the injured hepatocyte, disruption and extrusion of GGT into the canalicular region, and eventual absorption into the bloodstream. See excellent study by Irie et al:

"Hepatic expression of gamma-glutamyltranspeptidase in the human liver of patients with alcoholic liver disease" Hepatology Research (Nov 2007) 37(11):966-973. Abstract at: http://www.ncbi.nlm.nih.gov/pubmed/17854466

I cannot find a weblink for the full article. Here is Abstract:

Background: Gamma-glutamyltranspeptidase (GGT) has been recognized as an enzyme that converts glutathione into cysteine, and it is localized predominantly within the liver. Serum GGT is clinically recognized as the most useful marker for diagnosis of alcoholic liver disease (ALD). Methods: GGT localization within the liver was examined immunohistochemically using an anti-GGT antibody and was visualized by confocal laser scanning microscopy in ALD and normal livers. Double immunostaining for GGT and dipeptidylpeptidase-IV (DPP-IV) was carried out to evaluate GGT localization in greater detail. Results: Expression of GGT protein and mRNA was studied with immunoblot analysis and in situ hybridization, respectively. Immunohistochemically, the expression of GGT in the normal liver was faintly demonstrated in the bile canaliculi of hepatocytes and in biliary epithelial cells. In ALD livers, GGT was clearly demonstrated at the same sites. Double immunostaining demonstrated that GGT and DPP-IV were colocalized in hepatocytes in the ALD liver. In situ hybridization clearly demonstrated GGT-mRNA within the cytoplasm of hepatocytes and biliary epithelial cells. Immunoblot analysis revealed that GGT protein expression was increased in the ALD livers compared with that seen in the normal livers. Conclusion: These findings indicate that GGT in control and alcoholic livers is synthesized in hepatocytes and biliary epithelial cells, and is localized within the bile canalicular membrane and the luminal membrane in those cells, respectively. In conclusion, GGT synthesis and protein expression are increased in ALD livers, leading to the elevation of serum levels of GGT that are commonly noted in patients with the disease

For source of increased serum GGT in biliary cholestasis disorder, see Bulle at:

"Mechanism of gamma-glutamyl transpeptidase release in serum during intrahepatic and extrahepatic cholestasis in the rat: a histochemical, biochemical and molecular approach." in Hepatology. 1990 Apr;11(4):545-50 Abstract on web at:

http://www.ncbi.nlm.nih.gov/pubmed/1970323

I recommend the following article:

Serum {gamma}-glutamyltransferase: new insights about an old enzyme J. Epidemiol. Community Health. 2009;63:884-886

Thanks for all the comments and literature review. It really helped me.