GGT catalyzes the transfer of the γ-glutamyl group from peptides and other compounds to an acceptor. The enzyme acts only on peptides or peptide-like compounds containing a terminal glutamate residue joined to the rest of the com pound via the (γ)carboxyl terminus.
GGT is present (in descending order of abundance) in the renal proximal tubule, liver, pancreas, and intestine. The enzyme is present in the cytoplasm (microsomes), but the largest amount is localized in the cell membrane and can transport amino acids and peptides into the cell across its membrane in the form of γ-glutamyl peptides. GGT activity is also important for the maintenance of adequate intracellular concentrations of reduced glutathione, an important antioxidant agent.
Serum GGT activity derives primarily from the liver, where it is found predominantly in the biliary pole of the hepatocyte. However, it is also found in the cytoplasm and smooth endoplasmic reticulum (where the enzyme is susceptible to induction).
Clinical Significance
 Although renal tissue has the highest concentration of GGT, the enzyme present in serum comes primarily from the hepatobiliary system. GGT is a sensitive indicator of the presence of hepatobiliary disease, being increased in most individuals with liver disease regardless of cause, but its usefulness is limited by its lack of specificity. As in the case of ALP, it is higher in cases of intrahepatic or posthepatic biliary obstruction, reaching activities 5–30 times higher than URL. Marked increases in GGT are also observed in patients with primary or secondary (metastatic) cancers of the liver and other space-occupying liver lesions, presumably caused by intra hepatic obstruction. Moderate increases (two to five times the URL) occur in infectious hepatitis. Slight increases in GGT are observed in more than 50% of patients with NAFLD and similar but transient increases are noted in cases of drug intoxication. In acute and chronic pancreatitis and in some malignancies of the pancreas (especially when associated with hepatobiliary obstruction), enzyme activity may be 5–15 times higher than the URL.
Increased GGT activities are found in the sera of patients with alcoholic hepatitis and in most sera of heavy drinkers. GGT also increases with increasing body weight and in obese subjects. Increased concentrations of the enzyme are also found in the serum of subjects receiving anticonvulsant drugs, such as phenytoin and phenobarbital. Such an increase in serum GGT activity may reflect the induction of new enzymatic activity by alcohol and drugs or their toxic effect on the microsomal structures of the hepatocyte.
Unlike ALP, serum GGT is not increased in situations where osteoblastic activity is increased; therefore, measurement of the enzyme may be useful in differentiating the source of increased serum ALP activity, bone, or liver.
Epidemiological evidence has shown that serum GGT activity possesses an independent prognostic value for cardiovascular morbidity and mortality. This appears to be related to the ability of GGT to mediate redox/pro-oxidant reactions at the cellular level.
Reference Intervals
In adults, the URL of GGT in serum is 40 U/L for females and 68 U/L for males. In term infants, GGT activity at birth is ∼6–7 times the adult reference interval. The activity then decreases, reaching adult values between 5 and 7 months of age.