GGT is one of a large group of enzymes “Peptidases”. A membrane bound enzyme whose active site faces the external side of cell. Hepatobiliary tract enzyme.

1. γ-GLUTAMYL TRANSFERASE
(GGT)
Tapeshwar Yadav
(Lecturer)
BMLT, DNHE,
M.Sc. Medical Biochemistry

2. Other names :
γ-Glutamyl transpeptidase(GGTP),
γ-GT.

3. • GGT is one of a large group of enzymes
“Peptidases”.
• A membrane bound enzyme whose active site
faces the external side of cell.
• Hepatobiliary tract enzyme.

4. INTRODUCTION:-
→ GGT - γ - GT Catalyzes the transfer of γ - glutamyl
group from peptides or peptide like compounds to an
acceptor peptide molecule.
Eg:
γ - glutamyl P- Nitroanilide + Glycylglycine ⇔ P-nitroanilide +
( Substrate donor) ( Acceptor) γ - glutamylglycyl
glycine
(Transfer product)
GGT

5. →GGT acts only on peptides or peptide like
compounds containing a terminal glutamate residue
joined to the remained compound through the
terminal γ-carboxy.
→Glycylgycine is the five times more effective as an
acceptor than is either(Glycine or the tripeptide).
→The rate of peptidase transfer reaction is
considerably faster than that of simple hydrolysis
reaction.

6. → GGT plays a major role in glutathione
metabolism.
→ Leukotriene Synthesis
→ Drug
→ Xenobiotic detoxification

7. • SITE :
→Some enzymes is present in cytosol, but the
larger fraction is located in the cell membrane.
→ GGT found in many tissues like.
→ Highest tissue activity of this enzyme is found
in kidney.
→ Relatively high activity in canalicular portion of
hepatocyte, pancreas acinar, prostate, bile duct.

8. • FUNCTIONS :
→ It is involved in the transfer of Amino acids across
the cell Membrane.
→ Resorption of Amino acids from glomerular
filtrate and from the Intestinal Lumen.
→ In glutathione metabolism by transferring the
glutamyl moiety to a variety of acceptor molecule.

9. BIOCHEMICAL ROLE:
• Glutathione is a tripeptide
• Glutamyl-cysteinyl-glycine
• Synthesis occur in cytosol

10. GSH
GSH SYNTHETASE
ADP +PI
γ-GLU-CYS
ADP +PI
γ GLU-CYS SYNTHASE
GLUTAMATE
5-OXOPROLINASE
ATP ADP + PI
5 - OXOPROLINE
γ GLU Cyclo transferase
AMINOACID
γ GLU AMINOACID
GGT
AMINOACID
CYS - GLY
DIPEPTIDASE
CYS
GLY
GAMMA GLUTAMYL CYCLE
(Meister Cycle):

11. LEUKOTRIENE SYNTHESIS :
• Leukotriene- Conjugated trienes formed
from Eicosanoic acids in leucocytes by the
lipoxygenase pathway. In response to both
immunologic and non-inflammatory
stimuli.
• Synthesis-LTS are synthesized from
Arachidonate + Hydroxy peroxy groups to
arachidonic acid and produce Hydroxy
peroxy Eicosan tetraenoates (HPETE)

12. 5HPETE
Hydroxylase H2O
LTA4
Hydroxylase H2O
LTB4
Glutathione
LTC4
GGT Glutamate
LTD4
Cysteinyl-glycine dipeptidase Glycine
LTE4

13. • Xenobiotic Detoxification : Several
xenobiotics undergo detoxification by conjugation
to produce less toxic and or more easily
excretable compound.
• CONJUGATION : Foreign compound combines
with a substance produced in the body.
Eg: Glutathione
A wide range of organic compound get
conjugated with cysteine of glutathione. The
formation of mercapturic acid.

14. R-X + GSH
HX GSH transferase
R-SG
Glutamate GGT
Cysteinyl glycine
Glycine Cysteinyl glycine
Cysteine
AcetylcoA
N- Acetyl Transferase
COASH
Mercapturic acid

15. RELEASE OF ENZYME IN TO CIRCULATION :
→ Release of GGT into serum reflects the toxic effect of
alcohol & other drugs on microsomal structure in liver
cell.
→ Cell damage ↑ membrane permeability causing
cytosolic iso-enzymes to spill into the sinusoid and from
these into peripheral blood.
→ Fragment of hepatocyte membrane rich in GGT activity
this membrane fragmented by bile acids.
→ Bile acids acts as detergent, could solubilize and release
GGT from plasma membrane.

16. SIGNS AND SYMPTOMS OF LIVER DISEASES :
 Yellowish skin & Eyes.
 Light coloured stool.
 Dark coloured urine.
 Increase fatigue.
 Loss of appetite.
 Nausea and vomiting.
 Itching sensation.
 Pain and swelling in abdomen.

17. ESTIMATED METHODS:
→ GGT in diagnostic Enzymology dates from the
introduction in 1969 of a convenient method of assay
by “SZASZ”
→ Method and modifications of it use
→ L - γ glutamyl P-nitroanilide (Substrate)
→ Glycylglycine (acceptor) serving as the γ -glutamyl residue
acceptor.
→Other Substrates:- That have been investigated include the γ
-glutamyl derivatives of
→ aminopropionitrile.
→ α - Napthylamine
→ aniline

18. →GGPNA has been found to be most convenient because
it is very sensitive and the P-nitoraniline formed can be
directly measured.
→Derivatives of GGPNA are also available and have
been used in other methods. In these derivatives,
various groupd have been introduced into the ring to
increase solubility in water.
→The most useful substrate is L- γ - glutamyl 3-carboxy-
4-nitroanilide. Which is readily soluble in water and is
split by GGT at a rate comparable to that observed with
L-GGPNA.

19. DETERMINATION OF GGT:
• Carboxy substrate method (Kinetic method)
→ Sample - Serum free from hemolysis
Principle:
L-γ-Glutamyl 3-carboxy 4-nitroanilide L- γ-Glutamyl glycylglycine
+ +
Glycylglycine 5-Amino-2-nitrobenzoate
• The rate of formation of 5-amino 2-Nitrobenzoate is
measured as an increase in absorbance which is
proportional to the GGT activity in the sample.
GGT

20. Addition Sequence Test (ml)
Working reagent 1.0
Incubate at the assay
minute
temperature for 1
and add
Sample 0.1
PROCEDURE :- Pipette in to a clean dry test tube
Mix well and read the initial absorbance A0 after 1 minute.
wavelength at 405 nm on ERBA Chem-5.

21. Calculations :
GGT activity in U/L = ∆ A/min ×1158
Normal Values :
Males - 10-50 U/L
Females - 7-35 U/L

22. CLINICAL SIGNIFICANE :-
• The enzyme present in serum appears to originate
primarily from the Hepatobiliary system.
• GGT activity is elevated in all forms of liver disease
like
• Obstructive jaundice
– Cholangitis
– Cholecystitis
– Biliary atresia
– Infectious hepatitis

23. • GGT IN MI: It occurs at about the fourth day and
reaches a maximum value another 4th day and probably
implies liver damage secondary to cardiac insufficiently.
• GGT IN ALCOHOLICS: Elevated levels are observed
alcoholic cirrhosis.
• GGT IN RECEIVING DRUGS: Such as phenytoin
(Dilatin) & Phenobarbital raised levels of the (GGT) are
found in serum.
• GGT IN PANCREATITIS: Enzyme activity may be 5
to 15 times the upper limit of normal.
– Especially if associated with Hepatobiliary
obstruction.

24. • GGT IN PROSTATIC MALIGNANCY: Elevated
levels of GGT are observed. The activity of GGT in
sera of males is approximately 50% higher than in sera
from females.
• ELEVATED GGT IN: Primary & Secondary
metastatic neoplasms.
– Alpha 1-antitrypsin deficiency.
– Tumors.
– Anticonvulsant drugs.
– Acute uroneal infection.

25. DECREASED LEVELS OF GGT:
• Chronic renal failure
• Hypothyroidism
• Hypothalamic malfunctions

26. ADVANTAGES:
• Relatively high sensitivity and specificity
because of their measurement is easy and in
expensive.
• Elevated earlier in liver diseases.
• Early detection of chronic alcohol misuse.
• Enzyme level found correlate with the duration
of the drug action.

27. SUMMARY:
• GGT is the most sensitive enzyme indicator of
the Hepatobiliary disease.
• Normal values are rarely found in the presence
of liver disease.
• GGT is of little value in attempting to
discrimination between kinds of liver diseases.

28. Thank You