|Secondary to quaternary structure||Heterodimer, membrane protein|
|Substrate||5-L-glutamyl peptide + amino acid|
|Products||Peptide + 5-L-glutamyl amino acid|
γ-Glutamyltransferases ( γ-GT pronounced: 'Gamma-GT', GGT , also γ-Glutamyltranspeptidasen , γ-GTP ) are a group of enzymes in many body cells of mammals , fungi and bacteria . They are part of the defense against reactive oxygen species .
GGT transfers the glutamyl residue of glutathione to peptides or water. This simultaneously initiates the breakdown of glutathione (GSH). This degradation is the only way to smuggle the cysteine contained in GSH effectively and without loss into the cell, since there is no GSH membrane transporter . GSH is rebuilt within the cell.
The second reaction path, of which the reaction catalyzed by GGT is a part, is the discharge of foreign substances that have been bound in the cell by GSH (on the thiol group ). Here, the removal of the glutamate from the GSH part increases the transportability of the adduct so that it can be discharged .
Importance in medicine
Occurrence in humans
At least thirteen genes are known in humans which code for a GGT , of which at least six are active, each with several isoforms . Several isoforms of GGT are inactive in humans. One isoform of GGT7 binds to FAM57A. GGT5 converts leukotriene C4 to leukotriene D4 and shows a changed substrate affinity. GGT3 is found in some epilepsy patients.
UE1 + UE2 = total
|GGT1||P19440||380 + 189 = 569||3||612346||In the kidneys , liver , pancreas , stomach , intestines , placenta , lungs . Isoform 3 inactive. If mutated, glutathionuria .|
|GGT2||P36268||380 + 189 = 569||2||137181||In fetal / adult kidney and liver.|
|GGT3P||A6NGU5||380 + 188 = 568||1||-||Possibly inactive.|
|GGT5||P36269||387 + 998 = 586||2||137168||May not react with GSH but with GSH conjugate. Catalyzes leukotriene C4 = D4.|
|GGT6||Q6P531||? +? = 493||2||612341||The substrate is GSH conjugate.|
|GGT7||Q9UJ14||472 + 190 = 662||4th||612342||Ubiquitously in small amounts, except in epithelial cells of the respiratory tract . The substrate is GSH conjugate.|
In laboratory diagnostics , the activity of the GGT is determined from the plasma or the serum in order to clarify whether a liver or biliary tract disease is present. The reference range for measurements at 37 ° C (GGT37) according to IFCC is below 42 U / l for women and below 60 U / l for men.
The laboratory value GGT, which is measured in the blood , corresponds to the total enzymatic GGT activity, whereby it is assumed that measurable increases result exclusively from the destruction of liver cells , since it is an enzyme that is normally firmly bound to the cell membrane .
However, increased GGT values can have many causes and must be interpreted in connection with other laboratory values such as alkaline phosphatase , ALT / GPT , AST / GOT or bilirubin . Slight increases can occur from the use of certain medications or from chronic alcohol consumption. Stronger increases are found in chronic hepatitis , liver cirrhosis , liver metastases or damage to the liver from poisons , drugs, alcohol consumption or hereditary diseases such as myotonic dystrophy type 2 (DM2, PROMM). The highest GGT values are observed in diseases of the biliary tract ( cholestasis , cholangitis ), in acute hepatitis and in toxic liver damage.
In the human kidney, GGT occurs in the highest concentration in the proximal tubule. There it is localized on the membrane surface of the microvilli (brush border) of the epithelia, i.e. directed towards the lumen. The GGT occurs here in the combination of a so-called multi-enzyme complex, which u. a. an alanine aminopeptidase and alkaline phosphatase also belong. The multi-enzyme complex consists of about 5 to 10 nm large stalked "balls" ( knobs ), which disintegrate from the membrane ( shedding ) and in increased concentration in the urine even with early damage to the kidneys (ischemia, nephrotoxins, inflammation or kidney transplant rejection ) of the sick appear (tissue proteinuria, histuria). The kidney-typical GGT, a glycoprotein with a lectin affinity for ConA and wheat-germ agglutinin, can be extracted from the urine of patients with kidney diseases e.g. B. isolate by immunospecific affinity chromatography. The GGT is an important differentiation marker of tubular kidney cells, whereby the GGT biosynthesis is adapted depending on the kidney function: for example, hypertrophied (and hypermetabolic) nephrons in chronic kidney failure increasingly express membrane-bound GGT.
Renal adenocarcinoma: the membrane-bound GGT is - regardless of the tumor differentiation - a constant membrane marker of clear cell renal adenocarcinomas. A monoclonal antibody against a tumor-associated GGT, now also available recombinantly , was used for immunoscintigraphic purposes and immunohistological diagnosis of metastases.
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- Gamma-GT on med4you.at
- Gamma-GT measurement method published in CCLM ( Memento from September 16, 2004 in the Internet Archive ) (PDF; 71 kB)
- Stability in blood samples published by the WHO (PDF; 292 kB)
- Laborlexikon - trade journal for laboratory medicine: Gamma-GT
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- UniProt P19440
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- UniProt Q9UJ14
- UniProt P36269
- UniProt A6NGU5
- Lab Tests Online: GGT
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