γ-GTP Activity Research Articles

Lymphocyte gamma-glutamyltranspeptidase activity in ataxia-telangiectasia.

gamma-Glutamyltranspeptidase (GGTP) is a membrane-bound enzyme, that catalyzes gamma-glutamyl transfer from gamma-glutamyl compounds to amino acid and peptide acceptors. One of the most important clinical findings about ataxia-telangiectasia (A-T), a multisystemic and autosomal-recessive disease, is dysfunction of the immune system. In this study, the activity of GGTP was determined in the lymphocytes from patients with A-T. Lymphocyte GGTP activity in A-T patients was found to be significantly lower than that of control lymphocytes (P less than 0.001). This change may be due to the abnormality in the membrane of lymphocytes of A-T patients.

Effects of in utero administration of phenobarbital on γ-glutamyl transpeptidase

The present study was undertaken to determine the effects of the in utero administration of phenobarbital (Pb) on gamma glutamyl transpeptidase (γ-GTP) in rats. Female Wistar rats were bred to healthy adult males. On day 1 of gestation (evidenced by spermatozoa from vaginal smear) the pregnant rats were given 100 mg/kg phenobarbital (as the sodium salt) daily via the BioServ Liquid diet throughout gestation. Pair-fed controls were given the same volume of food as consumed by the experimental group. The offspring were sacrificed at birth and body, brain and liver weights determined. The pups born to the Pb treated mothers weighed significantly less than those born to the control mothers (4.77 and 6.60 g respectively). The brains and livers were homogenized in Tris buffered saline and assayed for γ-GTP activity. Brain γ-GTP activity was found to be 0.00807 u in the Pb group and 0.00670 u in the control group. We also examined the effects of chronic administration of Pb in adult rats and found no apparent effect on liver or brain γ-GTP activity.

Ultrastructure of Macrophages of Carrageenan Granuloma in the Rat With Data on Gamma-Glutamyltranspeptidase Activity

The present study is an electron-microscopic investigation of granuloma induced in the rat by the subcutaneous injection of 1% lambda-carrageenan in 0.8% sodium chloride. We report on the presence of desmosome-like structures connecting neighbouring macrophages. They consisted of electron-dense plaques, which are closely applied to the cytoplasmic surfaces of the junction. Usually, no bundles of cytoplasmic filaments attached to the plaques were seen. At the intercellular space at the level of the junction, a dense material was observed that was sometimes arranged in a cross-bridge fashion. The lysosomal system was markedly developed and consisted mainly of secondary lysosomes containing a filamentous material that showed intense acid phosphatase activity, which was also demonstrated in Golgi cisternae. A membrane preparation obtained from rat carrageenan granuloma contained gamma-glutamyltranspeptidase activity (GGTP), which is a cell and lysosomal membrane-bound enzyme. The GGTP activity of a similar membrane preparation of guinea pig carrageenan granuloma was six times higher than that of the rat.

Developmental changes in γ-glutamyl transpeptidase activity in nervous tissues with reference to amino acid transmission processes

In homogenate supernatants of hippocampal formation and cerebellum of the rat, γ-glutamyl transpeptidase (γ-GTP) activities increased about 6 times from postnatal day 6 (0.178 ± 0.02 and 0.187 ± 0.007 U/g wet wt., respectively) to day 100. In dorsal root ganglia (0.183 ± 0.003 U/g at day 6) and superior cervical ganglia (0.188 ± 0.019 U/g at day 6) in which apparently amino acidergic transmission processes do not occur, enzyme activities were seen to go up 4 times and 2.4 times, respectively. Based on protein, enzyme activities in both brain material and dorsal root ganglia showed a similar pattern, whereas the activity increase in superior cervical ganglia was somewhat gradual (1.4 times from day 6 to day 100). Postnatal changes in γ-GTP activities indicated a functional correlation with the maturation of amino acidergic structures. Kainic acid added to hippocampal extracts (0.45 and 5.0 mM) and, for comparison, to those of kidney (5.0 mM) did not yield any statistically significant effect on γ-GTP activity.

The Effects of Ethanol and Diet on Hepatic and Serum γ-Glutamyltranspeptidase Activities in Rats

Rats fed pelleted nonpurified diets had significantly higher hepatic γ-glutamyltranspeptidase (GGTP) activities than those fed liquid diets, with no difference in serum GGTP activities. However, levels of both hepatic and serum GGTP activity were higher in rats fed ethanol than in those fed liquid diets without ethanol. In addition, hepatic GGTP levels varied inversely with dietary carbohydrate content. These findings suggest that factors other than a mere increase of liver GGTP may be responsible for the elevated serum levels of this enzyme seen after chronic ethanol consumption and that dietary carbohydrate levels influence hepatic GGTP levels.

Biochemical markers of chronic alcoholism

Usefulness of several biochemical markers for the monitoring of chronic alcoholism were studied. Among generally used markers, only γ-GTP showed a significant difference between alcoholic and non-alcoholic liver diseases. Serum glutamate dehydrogenase (GDH) activity was significantly high in alcoholic liver disease. When the ratios of GDH to ornithine carbamyl transferase (OCT) were calculated, differences between alcoholic and non-alcoholic liver diseases became clearer without overlapping of any value. Serum desialo-transferrin was found in about 60% of the alcoholics, and disappeared by abstinence. Microheterogeneity of serum protein was also found in other glycoproteins. Serum prealbumin level was significantly high in alcoholics without severe liver disease. Acetaldehyde dehydrogenase (ALDH) activity of erythrocytes was significantly low in alcoholics, and gradually increased after abstinence. These results indicate that microheterogeneity of glycoproteins, serum prealbumin level and erythrocyte ALDH activity are good markers of alcohol abuse, and serum GDH/OCT ratio is the most sensitive marker of alcoholic liver injury. Serum γ-GTP activity is a good marker of both conditions.

γ‐Glutamyl Transpeptidase Activity and Its Serial Measurement in Differentiation Between Extrahepatic Biliary Atresia and Neonatal Hepatitis

The liver functions of 17 babies with extrahepatic biliary atresia (EHBA) and 19 babies with neonatal hepatitis (NNH) were analyzed. The serum γ‐glutamyl transpeptidase (GGTP) level and its rate of rise were significantly higher in the EHBA group. Both cross‐sectional and longitudinal studies showed a positive cor‐relation between the GGTP activity and the duration of the disease. The diagnostic accuracy is 79% for EHBA and 95% for NNH. It is suggested that GGTP and its rate of rise are the most important biochemical parameters in the differential diagnosis of these two diseases.

Microvillar enzyme analysis in amniotic fluid and the prenatal diagnosis of cystic fibrosis.

The activities of two microvillar enzymes, gamma-glutamyltranspeptidase (GGTP) and alkaline phosphatase (ALP) have been determined in amniotic fluid (AF) samples from 39 pregnancies with a 1-in-4 risk of cystic fibrosis. Seventeen of these were investigated prospectively. A reduced proportion of the fetal specific intestinal ALP isoenzyme was found in 7 of a total of 13 pregnancies with cystic fibrosis and in one pregnancy of confirmed normal outcome. Eight of the affected pregnancies were tested for AF GGTP activity and depressed levels were found in 15. None of the 3 liveborn cystic fibrosis cases in the prospective series was identified by the ALP assay although 2 had significantly reduced GGTP activity. There were several amniotic fluid samples from cases of cystic fibrosis, trisomy 18 and normal outcome which had discordant GGTP and ALP results. Four of the 6 cases of cystic fibrosis misclassified by the ALP assay had amniocentesis at 15 or 16 weeks gestation. Evidence is presented which confirms a previous suggestion that amniocentesis after 17 weeks gestation improves the predictability of the ALP isoenzyme assay for the prenatal diagnosis of cystic fibrosis.

Relationship between serum gamma-GTP and nutrient intakes

The purpose of this study is to make clear a comprehensive relationship between activity and fraction ratio of serum γ-GTP and nutrient intakes.These figures are taken from 267 young healthy male students excluding habitual users of alcohol.The results of the survey were as follows:1) There were no statistically significant correlation between serum γ-GTP activity and obesity indices. A high correlation was observed between percentage of γ-GTP (1) fraction and Rohrer index, Broca index. (p<0.01)2) Serum γ-GTP activity had no correlation with the nutrient intakes.3) The percentage of γ-GTP (1) fraction correlated significantly with dietary intakes of vitamin C, protein(g)/weight(kg), vitamin B2, and vitamin B1. (p<0.01)4) Multiple regression analysis showed that the variables which correlated best with the percentage of γ-GTP (1) fraction were dietary intakes of vitamin C, protein(g)/weight(kg), vitamin B1.5) It is possible to conclude from the results that activity of serum γ-GTP was not affected by nutrient intakes but percentage of γ-GTP (1) was closely related to it.

耳下せん内に発生したリンパ上皮性のう胞の１例

The histogenesis of the lymphoepithelial (so-called branchial) cyst has been a matter of speculation and controversy for some time. The most popular hypotheses implicate the branchial apparatus, the thymic duct, and parotid salivary gland inculusions in lymph nodes.Lymphoepithelial cysts occurring within the parotid gland are rare developmental anomalies.A lymphoepithelial cyst within the parotid gland in a 52-year-old man is reported.The patient had a six-month history of a gradually enlarging mass lesion anterior to his left ear. A parotid sialogram and computed tomographic examination revealed the presence of a mass lesion in the upper portion of the superficial lobe. The clinical diagnosis was benign parotid tumor. Under general anesthesia, excision was performed. Approximately 5 ml of yellowish fluid was removed and biochemical analysis revealed high activity of LDH and γ-GTP. Histologically, the cyst was lined with squamous epithelium or cuboid epithelium which was surrounded by lymphoid tissue with follicles.There has been no recurrence of the lesion to date, 16 months after operation.

Renal gallium accumulation in mice with acute immune complex glomerulonephritis

67Ga uptake and heparan sulfate (HS) content were investigated during the recovery of mouse kidney from acute immune complex glomerulonephritis induced by daily injections of bovine serum, and the binding of 67Ga to glomerular basement membrane (GBM) was studied in vitro. The results were as follows. 67Ga uptake in the kidney increased after the start of bovine serum injection, and peaked on the 20th day. The uronic acid content in 1.2 M NaCl-soluble fraction (which contained predominantly HS) and the hydroxyproline content (an index of collagen) were increased at the 10th day, reaching a maximum at the 20th day. This pattern of HS content was essentially the same as that of 67Ga accumulation in the kidney. Urinary protein and γ-GTP activity peaked at the 5th day, and these patterns were different from that of 67Ga uptake. 67Ga binding to GBM was significantly inhibited by treatments with HS-degrading enzyme (heparitinase), nitrous acid, trypsin or papain. However, the binding to GBM was unaffected by treatment with chondroitinase ABC. These results provide further evidence that the 67Ga-binding substance in tumor tissues and inflammatory lesions is probably HS.

Amniotic fluid microvillar enzyme activities in the early detection of fetal abnormalities.

Measurement of the microvillar enzymes, gamma-glutamyltranspeptidase (GGTP), aminopeptidase M (APM) and alkaline phosphatase (ALP), in amniotic fluid supernatant has been proposed as a method for the early prenatal diagnosis of cystic fibrosis. The activities of these enzymes in a series of other fetal abnormalities have now been examined. GGTP activities were below the 5th percentile in 28 out of 54 cases of trisomy 21 and 9 of 14 cases of trisomy 18, while APM values were below this cut-off in 26 of 54 cases of trisomy 21 and 8 of 14 cases of trisomy 18. Abnormal ALP isoenzyme ratios were found in 6 of 54 cases of trisomy 21 and 4 of 14 cases of trisomy 18. If prenatal cytogenetic studies are routinely carried out on amniotic fluid cells, the occasional confounding effect of abnormal microvillar enzymes associated with fetal trisomies rather than with cystic fibrosis should be avoided.

Intracellular content of thiol compounds, thiobarbituric acid reactive substances and gamma-glutamyl transpeptidase in rat brain during anoxia

Intracellular thiol compounds like glutathione play an important role in scavenging free radicals. Free radical reactions occur in the respiratory chain, and free radicals are known to accumulate in hypoxia and ischaemia. The content thiobarbituric acid (TBA) reactive substances, thiol and non-protein thiol (reduced glutathione) concentrations along with the activity of γ-glutamyl transpeptidase (GGTP), a membrane enzyme, were estimated in three regions of the brain in rats exposed to anoxia. It was observed that no change occurred in the content of TBA-reactive substances in any one of the three brain regions, although a significant increase in the non-protein thiol concentration occurred uniformly during anoxia. A significant increase in GGTP occurred in all the three brain regions during anoxia. The increase in the activity of GGTP is suggestive of an alteration in the function of blood-brain barrier during anoxia. These results are suggestive of an absence of lipid peroxidative damage during anoxia.

EFFECT OF 1, 25 DIHYDROXYCHOLECALCIFEROL (1, 25 D3) ON LEUKOCYTE GAMMA GLUTAMYL TRANSPEPTIDASE (GGTP)

GGTP is a membrane enzyme necessary in the transfer of some amino acids into the cytosol as a primary event in protein synthesis. Mechanisms of 1,25 D3 in promoting protein synthesis in corporal cells need further elucidation. Circulating leukocytes offer a readily accessible modality for assay of cellular enzyme activity. We, therefore, studied the effects of 1,25 D3 on growth and GGTP activity in young male Wistar rats. The animals were allowed ad libitum feeding of standard Purina Lab Chow during a period of 21 days. Vitamin D supplemented animals received daily injections of 50 pMol 1,25 D3 in 0.2 ml polyethylene glycol(PEG). Control animals were injected with 0.2 ml PEG alone. At sacrifice, leukocyte GGTP was assayed. Growth parameters and enzyme activity are shown below: (Mean± S.D.; *Indicates Difference p <0.05)A tenfold increase in GGTP activity was noted in 1,25 D3 supplemented animals. Our study suggests an induction of GGTP activity in leukocytes by 1,25 D3 which may, in turn, influence corporal protein synthesis.

GAMMA GLUTAMYL TRANSPEPTIDASE (GGTP) IN CHRONIC EXPERIMENTAL UREMIA

GGTP is a membrane enzyme facilitating amino acid transport into cells. We have studied the specific activity of the enzyme in young, growing rats rendered uremic by 7/8 nephrectomy. Results were compared to control animals fed either isocaloric diets (PC) or ad libitum diets (AC). Tissues were assayed for GGTP activity after 21 days of controlled feeding. Tissues included kidney, liver, intestinal mucosa and leukocytes. The following table summarizes the results (mean ± S.D.): The results demonstrate abnormally low GGTP in leukocytes of uremic rats. Kidney GGTP was higher than control values possibly on the basis of renal tubular injury. Malnutrition does not appear to significantly influence GGTP activity.

Gamma-glutamyltranspeptidase levels as an aid in the management of human cancer

Plasma gamma-glutamyltranspeptidase (GGTP) levels were measured in 435 cancer patients, 120 healthy controls, 15 patients with systemic lupus erythematosis, and 10 patients with rheumatoid arthritis. The mean GGTP activity of all cancer patients studied, with the exception of malignant lymphoma, was significantly elevated compared to control values. Several patient groups were retrospectively analyzed to determine whether GGTP levels correlated with clinical status. Patients who were disease-free had GGTP levels in the normal range, whereas patients with metastases had elevated levels. Serially increasing GGTP levels were associated with disease progression and death. Persons who remained free of disease had serial GGTP levels within the normal range. Furthermore, decreasing levels were associated with response to therapy. These results indicate that GGTP levels may have prognostic value in various human malignancies.

MICROVILLAR PEPTIDASE ACTIVITY IN AMNIOTIC FLUID: POSSIBLE USE IN THE PRENATAL DIAGNOSIS OF CYSTIC FIBROSIS

The activities of two microvillar peptidases, γ-glutamyl transpeptidase (GGTP) and aminopeptidase M (APM), have been measured in 132 samples of mid-trimester amniotic fluid. These included samples from 16 pregnancies at risk for cystic fibrosis. The activities of both peptidases were significantly below the normal range in amniotic fluids from the 6 affected pregnancies. This points to early pathological changes in fetal tissues in which microvilli are prominent. In contrast, 4-methylumbelliferylguanidinobenzoate-reactive protease activity in amniotic fluid from the 6 affected pregnancies was normal. Correlation of individual values between GGTP and APM was close in all cases examined, so that when a further 7 samples from cases at risk became available they were tested for GGTP alone. Of these, the 3 affected pregnancies had significantly reduced GGTP activity, particularly in the early weeks of gestation. It is suggested that early amniocentesis and examination of γ-glutamyl-transpeptidase isoenzyme constitution might make possible the reliable early diagnosis of cystic fibrosis.

γ-Glutamyl transpeptidase activity in liver disease: serum elevation is independent of hepatic GGTP activity

γ-Glutamyl transpeptidase activity was measured in liver and serum from 110 patients undergoing diagnostic liver biopsy, including patients with alcoholic liver disease, fatty liver not due to alcohol, primary biliary cirrhosis, persistent hepatic disease, chronic active hepatitis and normal livers. Serum γ-glutamyl transpeptidase was markedly elevated in patients with alcoholic liver disease and primary biliary cirrhosis while mean hepatic γ-glutamyl transpeptidase activity was significantly increased only in the alcoholic liver disease group. There was considerable overlap of individual enzyme values among the different disease groups. There were no inhibitors or activators of liver γ-glutamyl transpeptidase in any of these disorders. The increased liver activity was not related to the degree of hepatic fibrosis or cirrhosis. There was no correlation between hepatic and serum γ-glutamyl transpeptidase activity. Hepatic and serum gamma activities were equally increased in individuals with alcoholic liver disease whether or not they were drinking at the time of the study. The data suggest that increased hepatic γ-glutamyl transpeptidase activity is neither specific for alcoholic liver disease nor essential for serum GGTP to be elevated.

Studies on the Relationship of Levels of DNA and Gamma-Glutamyltranspeptidase Activity in Bronchial Secretions of Patients with Cystic Fibrosis with the Degree of Severity of Disease

Diana S. Leahy, B.S.;#{176}and Marinus Flux, M.D.t T he presence of excessive amounts of respiratory tract secretions with abnormal viscoelastic properties is the most widely known feature of cystic fibrosis (CF) . In general, the production and viscosity of these secretions appear to increase with increasing severity of the disease. The epithelial mucus glycoproteins and other soluble proteins present in bronchial secretions are, to a large extent, responsible for the viscoelastic properties of the normal bronchial secretions.1 Since bronchial secretions in cystic fibrosis contain increased amounts of DNA, protein and lipids as compared to secretions from normal controls,2,3 these components, in addition to mucus glycoproteins, may significantly influence the viscosity of CF secretions. The presence of increased levels of DNA and .y-glutamyltranspeptidase ( GGTP ) , ( a plasma membrane-bound glycoenzyme present in the bronchial mucosa4 and other tissues involved in absorption or secretion) has been reported to be indicative of obstructive pulmonary disease. In this work, we investigated the relationship of both the DNA content and the level of GGTP activity in the respiratory secretions of CF patients with the severity of disease.

Regulation of polyglutamate production in Bacillus subtilis (natto): Transformation of high PGA productivity.

Bacillus subtilis (natto) produces a considerable amount of polyglutamate (PGA). The genetic character of high PGA productivity of B. subtilis (natto) was transferred by DNA-mediated transformation to B. subtilis Marburg 168 which cannot produce PGA. The enzyme activity of γ-glutamyltranspeptidase (γ-GTP) of the three transformants, 3F1, F1-9 and M5B4, was 124, 233 and 147 mU/ml, which is about 25, 250 and 100% of that of the donor strains, respectively. However, other enzyme activities such as those of alanine racemase or transaminase among the parental strains and representative transformants were almost the same.These results suggested that γ-GTP activity might mainly participate in the biosynthesis of PGA in B. subtilis (natto).