Gamma (γ) Glutamyl Transpeptidase (GGT), Gamma glutamyl transferase

Sample

1. The venous blood is needed to prepare the serum.
2. The serum is stable for one month at 4 °C.
3. The serum can be stored for one year at -20 °C.
4. Heparinized samples interfere with various methods.

Purpose of the test (Indications)

1. This test is done for liver dysfunction.
2. This is also useful to detect alcohol-induced liver cell injury and chronic alcoholics.
3. This test can detect the slightest degree of cholestasis.
4. GGT is very sensitive to the biliary obstruction, cholangitis, and cholecystitis.
5. GGT is a good marker for pancreatic cancer, prostatic carcinoma, and liver cell carcinoma.
6. GGT level indicates remission and recurrence.

Precautions

1. Keep in mind that value may be low in late pregnancy.
2. Drugs that decreased the value are Clofibrate and oral contraceptives.
3. Drugs which increased the value are Alcohol, Dilantin, and Phenobarbital.
4. GGT is raised in patients who are taking antiepileptic drugs.

Pathophysiology

1. (γ) Glutamyl Transpeptidase is one of many peptidases cleaving terminal peptide bonds of proteins or peptides.
   1. The C-terminal amino acid must be glutamic acid.
   2. Specificity resides in the (γ) Glutamyl portion of the substrate.
   3. Three different reactions have been attributed to this enzyme:
      1. Hydrolysis.
      2. Internal transpeptidation.
      3. External transpeptidation.
   4. Glutathione is the common substrate of this enzyme in the body.
      1. This enzyme participates in amino acid transport by transferring the (γ) Glutamyl portion of glutathione to other amino acids, enabling them to cross cell membranes more easily.
2. According to concentration, GGT is present in:
   1. The proximal tubule of the kidney.
   2. Liver.
   3. Pancreas.
   4. Intestine.
   5. Prostate.
3. GGT is found in the epithelial cells of the biliary tree and mostly in the interlobular bile ducts and bile ductules. This is the reason that it is very sensitive to the biliary injury.
   1. GGT is present in the kidney, pancreas, spleen, heart, intestine, brain, and prostate gland.
   2. GGT level is higher in the men because of the additional amount due to the prostate.
   3. The kidney has a maximum amount but the liver is considered the normal source of serum activity.
   4. It is found throughout the hepatobiliary system and other tissues.
4. GGT is present in the microsomes of the cytoplasm and the cell membrane.

5. GGT takes parts in the transfer of the amino acid and peptides across the cell membrane.

6. The Very small amount detected in the endothelium of capillaries.
7. This test has been useful in the detection of a male in nearly-risk drinkers (Not in female).
   1. This is most applicable as part of an alcoholic screening program.
8. It is a more sensitive indicator of liver disease in children than is alkaline phosphatase.
9. This is a very sensitive test to tell liver cell injury and its correlation with the alkaline phosphatase level.
10. GGT is raised in acute myocardial infarction and the mechanism is not clear.
    1. If it occurs in the first 7 days then it may be due to liver insult.
    2. Otherwise, it is raised usually in 1 to 2 weeks.
11. However, its raised level is nonspecific because it is raised in cardiac, pulmonary, pancreatic, renal disorders, diabetes, and alcoholism.
12. GGT correlates with alkaline phosphatase in obstructive jaundice and metastatic infiltrate in the liver.
    1. In such a case, GGT is more sensitive and specific.
13. The overall clinical significance is limited.

• GGT normal with raised alkaline phosphatase indicates skeletal muscle disease.
• GGT raised with alkaline phosphatase indicates hepatobiliary disease.

Normal

Source 2

• Male and female age 45 years and older = 8 to 38 units/L  (8 to 38 IU/L)
  • Female younger than 45 years = 5  to 27 units/L (5 to 27 IU/L)
  • Old people = Slightly higher than the adults
• Newborn = 5 times higher than adults.
  • Child = Similar to adult level.

Another Source

• Male = 7 to 47 U/L.
• Female = 5 to 25 U/L.
• Newborn = 5 times higher than an adult.
  • Another reference
    • Adult male = up to 55 U/L.
    • Adult female = 38 U/L.
    • The newborn is 6 to 7 times higher than the adults.
      • It is like an adult after 5 to 7 months.

Raised levels are seen in:

1. Obstructive liver disease and posthepatic obstruction.
   1. This may reach 5 to 30 times the normal value.
2. Infectious hepatitis where the rise is 2 to 5 times the normal value.
3. Liver diseases like cirrhosis, space-occupying lesion.
4. The a mild increase in the fatty liver.
5. Infectious mononucleosis,
6. Renal transplant.
7. Hyperthyroidism.
8. Diabetes mellitus.
9. Pancreatitis.
   1. The increase maybe 5 to 15 times the normal value.
10. Myocardial infarction.
    1. The increase is mild and may occur after the fourth day of infarction and peak reaches in the next 4 days (another reference).
11. Alcohol ingestion
12. EBV infection in Infectious mononucleosis, cytomegalic viral infection, and Reye syndrome.

The decreased level is seen in:

• Hypothyroidism.

GGT values normal:

1. Bone disorder and bone growth.
2. Pregnancy.
3. Skeletal muscle disease.
4. Renal failure.

• GGT is the choice of the enzyme in the case of Alcoholism.
• Very good at monitoring liver disease. Its return to normal in liver disease is a very good indicator.

---