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At least 613 records · Page 34Linked to original sources
PubMed1970

Lecithin Biosynthetic Enzymes of Onion Stem and the Distribution of Phosphorylcholine-Cytidyl Transferase among Cell Fractions.

Enzymatic activities of the cytidine 5'-diphosphate choline pathway for lecithin biosynthesis were demonstrated in homogenates of onion stem (Allium cepa). Choline kinase activity was present in the postmicrosomal supernatant, with less than 3% sedimenting with the particulate fractions. Phosphorylcholine-cytidyl transferase was distributed among all fractions, and phosphorylcholine-glyceride transferase was predominantly found in the particulate fraction.The phosphorylcholine-cytidyl transferase activity of onion stem required a divalent ion (Mg(2+) or Mn(2+)) for activity, was inhibited by Ca(2+), and was specific for cytidine triphosphate, with optimal activity in the range pH 6 to 7. To evaluate the distribution among cell fractions, conditions of pH, cofactors, substrate, and assay were optimized for each fraction. One-third of the transferase activity sedimented with the mitochondria-proplastids fraction, and one-third was in the microsomal supernatant. The dictyosome fraction contained about 10% of the total activity but showed a greater specific activity than the other fractions. Similar results were obtained with homogenates from rat liver, in that purified Golgi apparatus fractions contained the highest phosphorylcholine-cytidyl transferase activity on a protein basis when compared with other cell fractions at pH 7.2.

Journal Article↗
PubMed1978

Subcellular Localization of Glycosyl Transferases Involved in Glycoprotein Biosynthesis in the Cotyledons of Pisum sativum L.

Subcellular membrane fractions from 21-day-old pea (Pisum sativum) cotyledons that have associated UDP-N-acetylglucosamine N-acetylglucosaminyl transferase and GDP-mannose mannosyl transferase activities have been isolated and identified. The rough endoplasmic reticulum (RER) is the principal location of glycosyl transferases involved in the assembly of lipid-linked sugar intermediates and glycoproteins. Antimycin A-insensitive NADH-cytochrome c reductase activity was used to identify RER at a density of 1.165 g/cc in sucrose gradients. The high proportion of RER in this fraction was confirmed by electron microscopy.Other mannosyl transferases are found at a density of 1.123 g/cc and 1.201 g/cc but these glycosyl transferases do not appear to be involved with the formation of lipid-linked sugar intermediates utilized in glycoprotein biosynthesis.

Journal Article↗
PubMed1985

Nuclear ADP-ribosyl transferase activity correlates with induction of P-450 monooxygenases by phenobarbital in rat liver microsomes.

The effect of phenobarbital treatment on the nuclear ADP-ribosyl transferase activity has been studied in parallel with microsomal cytochrome P-450 concentration and related mono-oxygenase activities, in rat liver. A marked activation of the ADP-ribosyl transferase was observed 24 h after phenobarbital administration. The chronological study performed between 0-6 days after phenobarbital treatment showed a sharp increase in this nuclear enzyme activity, to approximately equal to 270% of the control value produced in 48 h. The administration of 5'-methylnicotinamide in vivo, an inhibitor of ADP-ribosyl transferase activity in vitro, produced a decrease both of the induction of liver microsomal cytochrome P-450 mono-oxygenases and nuclear ADP-ribosyl transferase activity. The role of nuclear ADP-ribosyl transferase in the adaptative response of the liver cell to phenobarbital is discussed.

Aminopyrine N-Demethylase↗
PubMed1992

Effects of S-carboxymethyl-L-cysteine on pulmonary sialyl transferase activity in vitro, in healthy and in sulphur-dioxide-induced bronchitic rats.

S-carboxymethyl-L-cysteine (carbocysteine) improves the visco-elastic properties of bronchial mucus in vivo, possibly as a result of an increase in the relative proportions of sialomucins in bronchial mucus. Carbocysteine was therefore studied in vitro and ex vivo in both normal and bronchitic rats on pulmonary sialyl transferase, responsible for the addition of sialic acid to mucus glycoproteins. Bronchitis was induced in male Sprague-Dawley rats by repeated exposure to sulphur dioxide for two weeks. During this time they received either 500 mg kg-1 day-1 carbocysteine or its vehicle by the oral route. Rats not being exposed to SO2 received the same treatment. The animals were then killed, and subcellular fractions prepared by differential centrifugation of lung homogenates. Sialyl transferase was assayed using CMP-14C sialic acid as substrate and desialysed fetuin as exogenous acceptor. Enzyme activity was located in both the (Golgi-containing) 10,000 g and 100,000 g pellets with minor activity in the cytosolic supernatants. When tested in vitro between 10(-6) and 10(-3) M, carbocysteine had no effect on sialyl transferase activity in microsomes taken from healthy or bronchitis rats. Repeated administration of carbocysteine was without effect on the sialyl transferase activity in 10,000 g pellets taken from healthy rats. However, in bronchitic rats there was a small but statistically significant (P less than 0.05) increase in enzymic activity in the treated group compared to the animals receiving the vehicle. There was no difference in the activity of the microsomal enzyme compared to vehicle-treated controls in either healthy or bronchitic rats. We conclude that it is possible that an increase in sialyl transferase activity in a Golgi-containing fraction of bronchitic lungs could explain the relative increase in sialomucins in bronchitic subjects.

Animals↗
PubMed2005

Diketo hexenoic acid derivatives are novel selective non-nucleoside inhibitors of mammalian terminal deoxynucleotidyl transferases, with potent cytotoxic effect against leukemic cells.

Mammalian terminal deoxyribonucleotidyl transferase (TDT) catalyzes the non-template-directed polymerization of deoxyribonucleoside triphosphates and has a key role in V(D)J recombination during lymphocyte and repertoire development. More than 90% of leukemic cells in acute lymphocytic leukemia and approximately 30% of leukemic cells in the chronic myelogenous leukemia crisis show elevated TDT activity. This finding is connected to a poor prognosis and response to chemotherapy and reduced survival time. On the other hand, recent data indicated that TDT is not the only terminal deoxyribonucleotidyl transferase in mammalian cells. Its close relative, DNA polymerase lambda, can synthesize DNA both in a template-dependent (polymerase) and template-independent (terminal deoxyribonucleotidyl transferase) fashion. DNA polymerase lambda might be involved in the nonhomologous end-joining recombinational repair pathway of DNA double-strand breaks. In this work, we report the characterization of the mechanism of action of three diketo hexenoic acid (DKHA) derivatives, which proved to be extremely selective for the terminal deoxyribonucleotidyl transferase activity of DNA polymerase lambda and TDT. They seem to be the first non-nucleoside-specific inhibitors of mammalian terminal transferases reported. Moreover, the DKHA analog 6-(1-phenylmethyl-1H-indol-3-yl)-2,4-dioxo-5-hexenoic acid (RDS2119) was not toxic toward HeLa cells (CC(50) > 100 muM), whereas it showed significant cytotoxicity against the TDT(+) leukemia cell line MOLT-4 (CC(50) = 14.9 muM), thus having the potential to be further developed as a novel antitumor agent.

Cell Line, Tumor↗
PubMed1971

Glucosylation of teichoic acid: solubilization and partial characterization of the uridine diphosphoglucose: polyglycerolteichoic acid glucosyl transferase from membranes of Bacillus subtilis.

Polyglycerolteichoic acid:glucosyl transferase (TAG transferase), one of the three enzymes involved in the pathway leading to the glucosylation of teichoic acid in Bacillus subtilis 168, was investigated. During the early stages of the growth of B. subtilis, TAG transferase is predominantly a soluble enzyme found in the cytoplasm. As growth proceeds, the amount of soluble enzyme decreases and the proportion of insoluble, membrane-bound TAG transferase increases, reaching a maximal value at the close of the logarithmic phase. Data are presented which suggest that these are two forms of the same enzyme, or have some common component. The effects of chaotropic agents, such as sodium trichloroacetate and sodium perchlorate, on the cytoplasmic membrane were also studied. These data show that such compounds can effectively remove the TAG transferase from the membrane in a water-soluble form. A study of some of the physical properties of this solubilized enzyme suggests that there is little difference between the two forms of the enzyme. Experiments are described which indicate that the glucosyl transfer by both the membrane-bound and soluble enzymes is not mediated by lipids.

Bacillus subtilis↗
PubMed1999

Alternative splicing results in differential expression, activity, and localization of the two forms of arginyl-tRNA-protein transferase, a component of the N-end rule pathway.

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. The underlying ubiquitin-dependent proteolytic system, called the N-end rule pathway, is organized hierarchically: N-terminal aspartate and glutamate (and also cysteine in metazoans) are secondary destabilizing residues, in that they function through their conjugation, by arginyl-tRNA-protein transferase (R-transferase), to arginine, a primary destabilizing residue. We isolated cDNA encoding the 516-residue mouse R-transferase, ATE1p, and found two species, termed Ate1-1 and Ate1-2. The Ate1 mRNAs are produced through a most unusual alternative splicing that retains one or the other of the two homologous 129-bp exons, which are adjacent in the mouse Ate1 gene. Human ATE1 also contains the alternative 129-bp exons, whereas the plant (Arabidopsis thaliana) and fly (Drosophila melanogaster) Ate1 genes encode a single form of ATE1p. A fusion of ATE1-1p with green fluorescent protein (GFP) is present in both the nucleus and the cytosol, whereas ATE1-2p-GFP is exclusively cytosolic. Mouse ATE1-1p and ATE1-2p were examined by expressing them in ate1Delta Saccharomyces cerevisiae in the presence of test substrates that included Asp-betagal (beta-galactosidase) and Cys-betagal. Both forms of the mouse R-transferase conferred instability on Asp-betagal (but not on Cys-betagal) through the arginylation of its N-terminal Asp, the ATE1-1p enzyme being more active than ATE1-2p. The ratio of Ate1-1 to Ate1-2 mRNA varies greatly among the mouse tissues; it is approximately 0.1 in the skeletal muscle, approximately 0.25 in the spleen, approximately 3.3 in the liver and brain, and approximately 10 in the testis, suggesting that the two R-transferases are functionally distinct.

Alternative Splicing↗
PubMed1976

Serum glycoprotein: glycosyl transferase activity in patients with renal disease.

Glycoprotein: galactosyl and glycoprotein: sialic acid transferase activities were measured in the serum of patients with minimal lesion nephrotic syndrome, acute renal failure, and chronic renal insufficiency of varying severity. The activity of galactosyl transferase was elevated in all patients but one. Sialic acid transferase activity was increased in the patient group as a whole, but the magnitude of the increase was smaller and less predictable compared to the galactosyl transferase enzyme. The physiologic consequence of increased glycosyl transferase activity in serum is discussed.

Clinical Trials as Topic↗
PubMed2006

Tumoral calcinosis presenting with eyelid calcifications due to novel missense mutations in the glycosyl transferase domain of the GALNT3 gene.

CONTEXT: Familial tumoral calcinosis (TC) is a rare autosomal recessive disorder characterized by metastatic calcifications, often periarticular. Biochemical findings include hyperphosphatemia, high 1,25-dihydroxyvitamin D levels, and elevated tubular maximum for phosphate reabsorption per deciliter of glomerular filtrate (TmP/GFR). TC is caused by biallelic mutations of the genes encoding either fibroblast growth factor 23 (FGF23) or uridine diphosphate-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc transferase 3 or GALNT3). OBJECTIVE: The objective was to identify mutations in FGF23 or GALNT3 responsible for a mild TC phenotype by DNA sequencing and to determine serum FGF23 levels by ELISA. PATIENTS OR OTHER PARTICIPANTS: The subject was a 25-yr-old Caucasian woman with eyelid calcifications and biochemical features of TC. RESULTS: Eyelid biopsy revealed superficial dermis calcifications. There was no history of metastatic calcifications, mineral homeostasis abnormalities, or renal dysfunction. Biochemistry revealed normal levels of calcium, creatinine, PTH, and 25-hydroxyvitamin D, with elevated phosphorous, TmP/GFR, and high normal 1,25-dihydroxyvitamin D levels. Intact FGF23 was undetectable (< 3 pg/ml), whereas C-terminal FGF23 was elevated (698.2 RU/ml). Mutation detection revealed compound heterozygosity for two novel mutations in the glycosyl transferase domain of the GALNT3 gene. CONCLUSION: Previously reported GALNT3 mutations in TC have been null mutations. This study shows that missense mutations affecting the glycosyl transferase domain of GalNAc transferase 3 also cause TC. Elevated C-terminal FGF23 fragments with undetectable intact FGF23 suggest that the mutant enzyme lacks the ability to glycosylate FGF23 and that glycosylation by GalNAc transferase 3 is necessary for secretion of functional full-length FGF23.

Adult↗
PubMed1997

Sequence and expression of Drosophila myristoyl-CoA: protein N-myristoyl transferase: evidence for proteolytic processing and membrane localisation.

The enzyme N-myristoyl transferase transfers the 14 carbon fatty acid myristate to an N-terminal glycine residue in a small subset of cytoplasmic proteins. Many myristoyl proteins are components of cellular signalling pathways, some of which play important roles during embryonic development, for example protein kinase A. Thus, the function of N-myristoyl transferase is probably essential for embryogenesis and it is of some interest to study the enzyme in an organism with well understood developmental biology. In this paper we report the purification of a processed form of the Drosophila enzyme from peripheral membrane fractions of embryos by affinity chromatography to a protein containing leucine rich repeats. We have also isolated the Drosophila N-myristoyl transferase gene and determined its nucleotide sequence. The predicted amino acid sequence of the Drosophila enzyme is closely related to that of mammalian and fungal N-myristoyl transferases and residues essential for enzyme function are conserved. Our findings indicate that a fraction of Drosophila NMT is bound to the membrane and they are consistent with recent results for the human enzyme. We suggest that N-myristoyl transferase may be recruited to the membrane as part of a translational complex, perhaps by binding to p34 ribosome binding protein, a leucine rich repeat receptor of the microsomal membranes. We have also studied the expression pattern of the gene in the embryo by northern blot analysis and in situ hybridization. The transcripts appear to be uniformly distributed in the pre-cellular embryo but at later stages the RNA is barely detectable with these methods. However, from about stage 14, high levels of transcript are detected in a small number of randomly distributed cells of the central and peripheral nervous system.

Acyltransferases↗
PubMed2005

Development of farnesyl transferase inhibitors: a review.

Farnesyl transferase inhibitors are a new class of biologically active anticancer drugs. The exact mechanism of action of this class of agents is, however, currently unknown. The drugs inhibit farnesylation of a wide range of target proteins, including Ras. It is thought that these agents block Ras activation through inhibition of the enzyme farnesyl transferase, ultimately resulting in cell growth arrest. In preclinical models, the farnesyl transferase inhibitors showed great potency against tumor cells; yet in clinical studies, their activity was far less than anticipated. Reasons for this disappointing clinical outcome might be found in the drug-development process. In this paper, we outline an algorithm that is potentially useful for the development of biologically active anticancer drugs. The development of farnesyl transferase inhibitors, from discovery to clinical trials, is reviewed on the basis of this algorithm. We found that two important steps of this algorithm were underestimated. First, understanding of the molecular biology of the defective pathway has mainly been focused on H-Ras activation, whereas activation of K-Ras or other farnesylated proteins is probably more important in tumorigenesis. Inhibition of farnesylation is possibly not sufficient, because geranylgeranylation might activate K-Ras and suppress the effect of farnesyl transferase inhibitors. Furthermore, a well-defined proof of concept in preclinical and clinical studies has not been achieved. Integrating the proposed algorithm in future studies of newly developed biologically active anti-cancer drugs might increase the rate of success of these compounds in patients.

Animals↗
PubMed1995

Effects of prolactin on galactosyl transferase and alpha-lactalbumin mRNA accumulation in mouse mammary gland explants.

Studies were carried out to determine the possible mechanism(s) by which prolactin (PRL) stimulates alpha-lactalbumin and galactosyl transferase activity in cultured mouse mammary tissues. In earlier studies it was shown that the onset of the PRL stimulation of galactosyl transferase activity occurs between 4 and 8 hr after adding prolactin to cultured mouse mammary gland explants, and a maximum effect is evoked by 24 hr. In contrast, an effect of prolactin on alpha-lactalbumin activity occurred 24 hr after adding PRL to mammary gland cultures, but not at earlier times. In the present studies, it is shown that prolactin effects an increased tissue accumulation of mRNAs for both alpha-lactalbumin and galactosyl transferase after a 4 to 6 hr culture with prolactin. The lowest concentration of prolactin that stimulates the accumulation of both galactosyl transferase and alpha-lactalbumin mRNA is approximately 10 ng/ml, and a maximum response is achieved with 200 ng/ml. Thus, it is likely that the effect of PRL on the activity of galactosyl transferase is causally associated with the effect of prolactin on the accumulation of its mRNAs. However, the PRL stimulation of alpha-lactalbumin activity is not temporally associated with the tissue accumulation of the mRNA for alpha-lactalbumin.

Animals↗
PubMed1976

[The electrophoretic pattern of gamma-glutamyl transferase in serum and its alteration by chylomicrons (author's transl)].

Using the sera from 20 patients with elevated gamma-glutamyl transferase activity (EC 2.3.2.2) due to intra- or posthepatic cholestasis, the enzyme was separated into four bands by cellulose acetate foil electrophoresis. The gamma-glutamyl transferase pattern permitted no differentiation between intra- or posthepatic cholestasis. Protein and lipid electrophoresis was performed simultaneously for each serum. It was found that a gamma-glutamyl transferase band, which appeared at the origin in 11 sera, was only observed in lipaemic sera containing chylomicrons. This band of gamma-glutamyl transferase does not, however, represent a true isoenzyme, because it results from a complex between chylomicrons and gamma-glutamyl transferase, which is separated with the chylomicrons, or is produced by the mixing of sera.

Bile Ducts↗
PubMed1975

Acetoacetate coenzyme A transferase activity in rat hepatomas.

The presence of succinyl-coenzyme A:acetoacetate CoA transferase (CoA transferase) (EC 2.8.3.5), an initiator of ketone body utilization in nonhepatic tissue, was examined in liver from normal, partly hepatectomized, neonatal, and tumor-bearing rats, as well as in a series of transplantable rat hepatomas ranging widely in growth rate. While levels of CoA transferase are extremely low in normal, host, and regenerating liver, considerable amounts of activity are detectable in neonatal liver and in the hepatomas. In fact, the content of CoA transferase in the series of Morris hepatomas increases progressively with increase in tumor-growth rate. The fastest-growing tumor studied (7288Ctc) contains about the same amount of CoA transferase activity as rat skeletal muscle (i.e., an activity of about 0.1 mumole of acetoacetate used per min per g tissue). These results clearly indicate that the faster-growing hepatomas have adequate capacity to utilize ketone bodies in bioenergetic or biosynthetic activities. Furthermore, the enzymes from normal and hepatoma 7288Ctc tissues are quite similar with respect to (a) size of about 10(5) daltons, (b) reaction mechanism requiring formation of an enzyme:CoA intermediate (from ping-pong kinetic data), and (c) various kinetic parameters (such as Michaelis constants, product competitive inhibition constants, and acetoacetate substrate inhibition). The enzymes from rat skeletal muscle and Morris hepatoma 7288Ctc have the same isoelectric point (7.6), which differs from that for the rat heart enzyme (6.8).

Acetoacetates↗
PubMed1989

Fat distribution and gamma-glutamyl transferase in relation to serum lipids and blood pressure in 38-year old Dutch males.

In this study we describe the associations between indicators of fatness, fat distribution, and alcohol consumption (gamma-glutamyl transferase) with serum lipids and blood pressure in a random selected group (n = 69) of 38-year old men. Waist circumference, subscapular skinfold and body mass index all had similar positive associations with total cholesterol, triglycerides and diastolic blood pressure. Gamma-glutamyl transferase levels were associated with indicators of fatness and fat distribution (waist circumference, waist/hip ratio, body mass index, and subscapular skinfold) and serum lipids (total cholesterol, LDL-cholesterol, triglycerides). Gamma-glutamyl transferase and body mass index both made independent contributions to the explanation of the waist/hip ratio. In multiple regression analysis, gamma-glutamyl transferase levels were (after adjustment for waist/hip ratio and body mass index) associated with serum lipids (total cholesterol, LDL-cholesterol, and triglycerides), but not with HDL-cholesterol and blood pressure. Body mass index only showed an independent relation to triglyceride levels, whereas the waist/hip ratio was only associated with diastolic blood pressure in multiple regression. It is concluded that gamma-glutamyl transferase levels are a potentially important indicator of abdominal fat distribution and unfavourable lipoprotein profiles.

Adipose Tissue↗
PubMed1988

Glutathione S-transferase distribution and concentration in human organs.

The concentration of basic, near-neutral and acid GSH S-transferase was measured in 18 organs from each of 9 male human subjects using radial immunodiffusion. Basic transferases were detectable in all tissues studied. Highest concentrations were found in liver, testis, kidney, adrenal and jejunum while low levels were found in bladder, muscle and thyroid. The concentration in liver was 230 times higher than that in thyroid. Near-neutral GSH S-transferase were absent in all tissues in 5 of the 9 individuals studied. When present they were widely distributed, highest concentrations being found in liver, testis, muscle, adrenal and brain and lowest levels in thyroid, lung, duodenum, stomach, heart and kidney. Acid GSH S-transferases were present in every individual studied although they were undetectable in the liver of a single subject. Highest concentrations were present in colon, jejunum, ileum, bladder, spleen and lung while low concentrations were found in liver. Our study provides conclusive evidence of marked inter-individual and inter-organ variation of the three groups of human GSH S-transferase.

Humans↗
PubMed1981

[Gammaglutamyl-transferase activity in human semen. Application to fertility studies (author's transl)].

The enzymatic activity of gammaglutamyl-transferase was measured in the semen of 79 male subjects undertaking fertility studies. The mean value obtained at 30 degrees C was 4898 +/- 2185 (mean +/- SD), which is 250 times the normal mean value in serum measured under identical conditions. No significant correlation was found between gammaglutamyl-transferase activity and sperm density, active lineal motility, and number with normal motility. Nor was a correlation found between gammaglutamyl-transferase activity and the concentration of citric acid, a marker of prostatic function, or fructose, a marker of seminal vesicle function. Very high levels of gammaglutamyl-transferase (25,000 and 16,850 U/l), and of citric acid (4,000 and 3,500 mg/dl) were found in two cases of excretory azoospermia, indicating that the prostate is probably the main origin of the enzyme, as described by other authors. Therefore, gammaglutamyl-transferase enzymatic activity could be utilized as a parameter of prostatic function in studies of male fertility.

Citrates↗
PubMed1983

Role of ADP-ribosyl transferase in differentiation of human granulocyte-macrophage progenitors to the macrophage lineage.

Nuclear adenosine diphosphate-ribosyl (ADP-ribosyl) transferase is a chromatin-bound enzyme catalyzing the transfer of ADP-ribose from NAD+ to chromatin proteins. The physiologic function of this covalent modification of chromatin has not been fully established, but roles in both DNA repair and in differentiation have been proposed. We demonstrate that three specific inhibitors of ADP-ribosyl transferase (5-methylnicotinamide, 3-methoxybenzamide, 3-aminobenzamide) inhibit differentiation of human granulocyte-macrophage progenitor cells to the macrophage lineage. Differentiation to the neutrophil-granulocyte lineage is much less affected. The inhibition of macrophage differentiation seems to relate to the ability of these compounds to inhibit ADP-ribosyl transferase. A structural analogue (3-methoxybenzoic acid), which is not inhibitory for the enzyme, did not inhibit macrophage differentiation. Additional evidence for a role of ADP-ribosyl transferase in the differentiation of granulocyte-macrophage progenitors was obtained from experiments in which enzyme activity levels were measured in permeabilized marrow cells. Marrow cell ADP-ribosyl transferase activity increased after 3-hr stimulation by the differentiation/proliferation stimulus--granulocyte-macrophage colony-stimulating activity (GM-CSA). Unstimulated marrow cells showed low or undetectable levels of enzyme activity.

Benzamides↗