Publisher Summary This chapter discusses the measurement of the serum γ-glutamyl transpeptidase (GGTP) in the clinical laboratory and its application to diagnosis. The enzyme GGTP catalyzes the transfer of γ-glutamyl groups from γ-glutamyl peptides to other peptides, to L-amino acids, and to water. The possible biological functions of GGTP include participation in peptide–nitrogen storage, in protein synthesis, in the regulation of tissue glutathione levels, and in the amino acid transport across cell membranes. The majority of GGTP determination procedures utilize Tris as buffer and γ-glutamyl p-nitroanilide as substrate. The automated p-nitroanilide method for the GGTP determination utilizes a continuous flow technique at 37°C using the Autoanalyzer II. The GGTP determination is of limited value for the diagnosis of myocardial infarction because of the high incidence of false positive and false negative values. The incidence and degree of plasma GGTP changes are correlated with a drug's ability to promote the hepatic enzyme induction. Enzyme changes may be dose or duration dependent, and individuals may show variation in enzyme changes consequent upon genetic variations in drug metabolism.

Gamma-glutamyl transpeptidase.

Rat liver canalicular membrane vesicles. Isolation and topological characterization.

By catalyzing the reaction of electrophilic compounds with the sulfhydryl group of glutathione, the glutathione S‐transferases play physiologically important roles in the detoxication of potential alkylating agents. The glutathione S‐conjugates thus formed are transported out of cells for further metabolism by γ‐glutamyltransferase and dipeptidases, ectoproteins that catalyze the sequential removal of the glutamyl and glycyl moieties, respectively. These ectoproteins are not found in all cells, but are localized predominantly to the apical surface of epithelial tissues. The resulting cysteine S‐conjugates can be reabsorbed by specific cell types, and acetylated on the amino group of the cysteinyl residue by intracellular N‐acetyl‐transferases, to form the corresponding mercapturic acids (N‐acetylcysteine S‐conjugates). Mercapturic acids are then released into the circulation and delivered to the kidney for excretion in urine, or they may undergo further metabolism. Mercapturic acid biosynthesis is general...

Glutathione conjugation and conversion to mercapturic acids can occur as an intrahepatic process.

Although it is now 30 years since the discovery of y-glutamyl transferase (EC 2.3.2.2.), the clinical relevance of a raised activity of the enzyme in serum remains controversial. The use of the enzyme as a potential diagnostic aid did not emerge until the early 1960s, when it was introduced as a new test of liver function.1 2 Further work since then suggests that serum y glutamyltransferase activity may be a sensitive index of hepato biliary dysfunction,3 and the early prediction that measurement of y-glutamyltransferase activity would be established in the laboratory repertoire seems to have been fulfilled.4 The associa? tion between excessive alcohol consumption and raised activities of serum y-glutamyltransferase, particularly in the absence of other abnormal results of biochemical tests of liver function, was made in the early 1970s, and a serum y-glutamyltransferase estimation has been included in many screening programmes to detect an excessive intake of alcohol.5 6 It is rare, however, to find a biochemical test that is both tissue specific and disease specific, and y-glutamyltransferase activity appears to be no exception. The serum activity of the enzyme has been shown to be affected by several factors and to rise in various clinical conditions. Also its induction by a wide variety of drugs, including alcohol, makes interpretation of test results difficult. Consequently, the claimed advantage of its sensitivity is marred by its lack of specificity. Recently, doubts

https://www.bmj.com/content/bmj/286/6364/531.full.pdf

Valma J. Child

Papers

Observations on the site of origin of serum γ-glutamyl-transpeptidase