Gamma-glutamyl transferase or gamma-glutamyl transpeptidase is an enzyme that transfers
gamma-glutamyl functional groups. It is found in many tissues, the most notable one being
the liver, and has significance in medicine as a diagnostic marker.
GGT catalyzes the transfer of the gamma-glutamyl moiety of glutathione to an acceptor that
may be an amino acid, a peptide or water. GGT plays a key role in the gamma-glutamyl
cycle, a pathway for the synthesis and degradation of glutathione and drug and xenobiotic detoxification.
Other lines of evidence indicate that GGT can also exert a prooxidant role, with regulatory
effects at various levels in cellular signal transduction and cellular pathophysiology.
Function 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
Structural studies In prokaryotes and eukaryotes, it is an enzyme
that consists of two polypeptide chains, a heavy and a light subunit, processed from
a single chain precursor by an autocatalytic cleavage. The active site of GGT is known
to be located in the light subunit. Medical applications
GGT is predominantly used as a diagnostic marker for liver disease in medicine, latent
elevations in GGT are typically seen in patients with chronic viral hepatitis infections often
taking 12 months or more to present. 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 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. 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 in fact accumulates in atherosclerotic
plaques, suggesting a potential role in pathogenesis of cardiovascular diseases, and circulates
in blood in the form of distinct protein aggregates, some of which appear to be related to specific
pathologies such as metabolic syndrome, alcohol addiction and chronic liver disease. High
body mass index is associated with type 2 diabetes only in persons with high serum GGT.
GGT is elevated by large quantities of alcohol ingestion. Determination of total serum GGT
activity is however not specific to alcohol intoxication, and the measurement of selected
serum forms of the enzyme offer more specific information. Isolated elevation or disproportionate
elevation compared to other liver enzymes may indicate alcohol abuse or alcoholic liver
disease. It may indicate excess alcohol consumption up to 3 or 4 weeks prior to the test. The
mechanism for this elevation is unclear. Alcohol may increase GGT production by inducing hepatic
microsomal production, or it may cause the leakage of GGT from hepatocytes.
Numerous drugs can raise GGT levels, including barbiturates and phenytoin. GGT elevation
has also been occasionally reported following NSAIDs, St. John's wort, and aspirin. Elevated
levels of GGT may also be due to congestive heart failure.
Individual test results should always be interpreted using the reference range from the laboratory
that performed the test though example reference ranges are 15-85 IU/L for men, and 5-55 IU/L
for women. Human proteins
GGT1; GGT2; GGT6; GGTL3; GGTL4; GGTLA1; GGTLA4; References
External links MedlinePlus Encyclopedia 003458
gamma-Glutamyltransferase at the US National Library of Medicine Medical Subject Headings
GGT - Lab Tests Online