Serum biliary enzymes usually reflect the obstruction of biliary tract and damages with the biliary capillaries.
All these four serum enzymes rise mainly with different proportions in biliary tract obstruction.
Clinically, the rise in serum levels is also observed in cases with hepatocellular damages.
Of these four biliary enzymes, alkaline-phosphatase and gamma-glutamyl transpeptidase are usually used in clinical practice.
Gamma-glutamyl transpeptidase:
Glutathione (gamma-glutamylcysteinyl-glycine) is one of the peptides that can be hydrolized by this enzyme, thus GGTP is also named as glutathionase at first.
GGTP not only catalyzes the hydrolysis of glutathione but also catalyzes the hydrolysis of other gamma-glutmyl peptides bonds and the transfer of gamma-glutamyl group from donor peptides to suitable acceptors, therefore it was named as gamma-glutamyl transpeptidase later.
Serum GGTP was first reported by Szewzuk and Orlowski in 1960 as a clinical diagnostic procedure in the diagnosis of hepatic diseases using the synthetic substrate alpha-(N-gamma-DL-glutamyl)-aminonitrile by colorimetric method, and later similar results were reported by Goldbarg with another synthetic substrate N-(DL-gamma-glutamyl)-aniline in 1963 and by Oikawa with the method of Szewczuk in 1964. Afterwards, it has been used mostly as the marker of biliary obstruction.
Author began the study of animal experiment and clinical evaluation of the serum GGTP determination in 1968, and reported the clinical usefullness of serum GGTP determination in the diagnosis of liver diseases in 1972. After 25 years of clinical experience, I am still confident on the value of clinical application of serum GGTP determination.
In Taiwan, the NTUH laboratory first applied the test as one of the routine work-up items in clinical practice in 1977, and up to date it has been one of the routine blood biochemical tests in almost all of the hospitals on the island. However, there are a few doctors who are still not familiar with the usefulness of this test.
By the report of Orlowski, the human body contains GGTP by 2,200 units in kidney, 180 u in pancreas, 85 u in liver, 35 u in spleen, 20 u in small intestine, 10 u in brain and 1 u in heart, therefore the ratio of GGTP content is 100 : 8 : 4 for kidney, pancreas and liver.
The biological significance of GGTP still remains to be clarified, thus we still do not know the reason why no rise in serum GGTP is observed in renal disease.
RBC contains no GGTP, thus the hemolysis does not affect the result of determination.
GGTP is rather stable enzyme; thus at -20 C, it is stable for one year; at 24 C, stable for 2 days, but at 38 C, only one day.
The value determined usually differs by the method and substrate used.
The reference value obtained by author using N-(DL-gamma-glutamyl)-aniline as substrate were:
Male: 4 - 52 U/L (28 ¡Ó 12)
Female: 4 - 40 U/L (22 ¡Ó 9)
Because of its greater individual difference on determination, it is advised to take
M ¡Ó 3 SD as its range of referance value.
No diurnal change, nor change by exercise or kinds of food was observed.
However, individual difference is rather remarkable. It differs depending on age, sex, habit of alcohol intake, and medication.
Higher value in fetus and newborn is noted.
Lower value are obtained among children and young peolple.
Women have lower serum levels than men, and during the pregnancy it would not rise even in the cases that it usually would elevate.
Abnormal serum values in diseases:
All three biliary enzymes elevate in the obstruction of biliary tract regardless of the size or caliber , and even elevate in the obstruction of bile canaliculi.
Hepatocytes damages usually show mild to moderate degree of elevation, thus in acute or chronic hepatitis they will show mild to moderate degree of elevation.
In space-occuping lesion of the liver, they will also increase, and when they increase in cases with normal serum bilirubin level, they are of specific diagnostic usefulness.
In the cases with isolated elevation of GGTP without accompaning increase of Al-P and LAP, an alcoholic drinking or the intake of medicines which would induce the enzyme release should be considered.
The elevation GGTP caused by alcohol drinking usually decreases to half of the original value within two weeks after abstinece.
An isolated elevation of Al-P was usually observed in children before maturation of bone growth and during bone repairement after a fracture in the adults.
In pregnancy, the concurrent elevation in Al-P and LAP are usually observed.
