Gamma glutamyl transpeptidase

The gamma glutamyl transpeptidase (γ-glutamyl-transferase, γ-GT, GGT, GGTP) (EC (Enzyme Commission Number) 2.3.2.2) is a liver enzyme. Its blood level can be measured, and despite existing in a large number of tissues, its presence predominates at the level of hepatocytes, being a laboratory marker of liver disease.

GGT catalyzes the transfer of a gamma-glutamyl portion of glutathione to an acceptor that can be an amino acid, a peptide, or a water molecule (formation of glutamate, a neurotransmitter). GGT plays a key role in the gamma-glutamyl cycle, a pathway for glutathione synthesis and degradation and for drug and xenobiotic detoxification.

Function

GGT is present in the cell membranes of many tissues, including the kidneys, bile duct, pancreas, liver, spleen, heart, brain, and seminal vesicles, as are transaminases and lactate dehydrogenase. It is involved in the transfer of amino acids through the cell membrane and the metabolism of leukotrienes. Its main role is in glutathione metabolism by transferring the glutamyl moiety to a variety of acceptor molecules such as water, some L-amino acids and peptides, leaving the cysteine product to preserve intracellular homeostasis from oxidative stress. In general the reaction is:

(5-L-glutamil)-peptide + amino acid {displaystyle rightleftharpoons } peptide + 5-L-glutamil-amino acid. Glutathion (5-L-Glutaminil-cysteinyl-glycin) + an amino acid = Cisteinyl-glycin + 5-L-Glutamil-amino acid

Use in medicine

GGT has several uses as a diagnostic marker in the clinic. In general, and depending on the laboratory in question, the normal range of the enzyme in the blood is from 6 to 28U/L. Elevated serum GGT values can be found in diseases of the liver, pancreas, and bile duct. Being elevated together with alkaline phosphatase, the diagnosis strongly points to bile duct disease. It is not yet known exactly whether GGT has greater sensitivity for cholestatic disease compared to alkaline phosphatase. The usefulness of the elevation of GGT lies in ruling out that the increase in alkaline phosphatase does not come from some bone pathology.

GGT also rises after excessive alcohol consumption. Isolated or disproportionate elevations compared to the elevation of other liver enzymes may indicate alcohol abuse or alcoholic hepatitis. The increase can remain even 3-4 weeks after intake. The mechanism by which this increase occurs is unknown. Alcohol can either increase GGT synthesis via microsomal induction or enzyme efflux directly from hepatocytes.