Gamma-glutamyl transpeptidase
γ - glutamyl transferase ( γ -GT, GGT, and γ -glutamyl transpeptidase, γ -GTP pronounced, gamma - GT ' ) is an enzyme in many body cells of mammals, fungi and bacteria. It is part of the defense against reactive oxygen species.
Biochemical function
GGT transfers the glutamyl residue of GSH to peptides or water. Thus, the degradation of GSH is initiated simultaneously. This reduction is the only way to smuggle the cysteine contained in GSH effectively and without loss in the cell because there is no GSH - membrane transporters. Within the cell, GSH is rebuilt.
The second pathway of the catalyzed reaction of GGT is a part, the rejection of foreign substances, which have been in the cell of GSH bound ( to the thiol group ). Here the removal of glutamate by GSH part increases the portability of the adduct, so that it can be discharged.
Importance in medicine
GGT serves as a marker, indicative of liver disease in combination with other values. Increased GGT occur in biliary atresia and bacteremia.
Elevated GGT levels correlate with an increased risk for subsequent type 2 diabetes and cardiovascular disease, as well as with elevated homocysteine concentration.
Mutations of GGT may cause the (rare ) Glutathionurie.
Occurrence in man
In humans, at least thirteen genes are known that encode for a GGT, of which at least six are active, each with several isoforms. Several isoforms of GGT are inactive in humans. An isoform of GGT7 binds to FAM57A. GGT5 converts leukotriene C4 to leukotriene D4 by showing altered substrate affinity. GGT3 is found in some patients with epilepsy.
Laboratory diagnostics
Liver diagnostics
In the laboratory diagnostics, the activity of GGT from the plasma or serum is determined in order to clarify whether a liver or biliary tract disease is present. The reference range for measurements at 37 ° C ( GGT37 ) IFCC is less than 42 U / l for women and 60 U / l for men.
The laboratory value of GGT, which is measured in the blood corresponds to the enzymatic GGT total activity, where one assumes that measurable increases are driven solely by destruction of liver cells, since it is an enzyme that is normally tightly bound to the cell membrane.
However Elevated GGT can have many causes and must be interpreted in conjunction with other laboratory values such as alkaline phosphatase, ALT / GPT, AST / GOT or bilirubin. Slight increases may occur by the ingestion of certain drugs or by chronic alcohol consumption. Stronger increases are found in chronic hepatitis, liver cirrhosis, liver metastases or liver damage by toxins, drugs, alcohol consumption or genetic diseases such as myotonic dystrophy type 2 ( DM2, PROMM ). The highest GGT observed in diseases of the bile ducts ( cholestasis, cholangitis ), acute hepatitis and in toxic liver injury.
Renal diagnostics
In the human kidney GGT is the highest concentration present in the proximal tubule. There is on the surface of the membrane microvilli ( brush border ) of the epithelia, so directed downward volume, isolated. The GGT occurs here in the composite of a so-called multi-enzyme complex, which among other things also an alanine aminopeptidase and alkaline phosphatase belong. The multi-enzyme complex consists of about 5 to 10 nm stalked " balls " (English knobs ) that even at early injurious to the kidneys ( ischemia, nephrotoxins, inflammation or renal transplant rejection ) of the membrane disintegrate ( shedding ) and in elevated concentrations in the urine the patients appear ( Gewebsproteinurie, Histurie ). The typical kidney GGT, a glycoprotein with a lectin affinity to ConA and wheat germ agglutinin - can be produced from the urine of patients with renal diseases such as isolated by immune -specific affinity chromatography. The GGT is an important differentiation markers of tubular kidney cells, the GGT biosynthesis is adjusted according to renal function: as expressing hypertrophied ( and hypermetabolic ) nephrons in chronic renal failure increased membrane-bound GGT.
Nierenadeno carcinoma: the membrane-bound GGT is - regardless of tumor differentiation - a constant membrane marker Nierenadeno clear cell carcinomas. A monoclonal antibody against a tumor-associated GGT now also available recombinantly, was used for purposes immunszintigrafische and immunohistological diagnosis of metastases.