Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oxidative metabolism of glutamine in HeLa cells was investigated using intact cells and isolated mitochondria. The concentrations of the cytoplasmic amino acids were found to be aspartate, 8.0 mM; glutamate, 22.2 mM; glutamine, 11.3 mM; glycine, 9.8 mM; taurine, 2.3 mM; and alanine, < 1 mM. Incubation of the cells with [14C]glutamine gave steady-state recoveries of 14C-label (estimated as exogenous glutamine) in the glutamine, glutamate, and aspartate pools, of 103%, 80%, and 25%, respectively, indicating that glutamine synthetase activity was absent and that a significant proportion of glutamate oxidation proceeded through aspartate aminotransferase. No label was detected in the alanine pool, suggesting that alanine aminotransferase activity was low in these cells. The clearance rate of [14C]glutamine through the cellular compartment was 65 nmol/min per mg protein. There was a 28 s delay after [14C]glutamine was added to the cell before 14C-label was incorporated into the cytoplasm, while the formation of glutamate commenced 10 s later. Aspartate was the major metabolite formed when the mitochondria were incubated in a medium containing either glutamine, glutamate, or glutamate plus malate. The transaminase inhibitor AOA inhibited both aspartate efflux from the mitochondria and respiration. The addition of 2-oxoglutarate failed to relieve glutamate plus malate respiration, indicating that 2-oxoglutarate is part of a well-coupled truncated cycle, of which aspartate aminotransferase has been shown to be a component [Parlo and Coleman (1984): J Biol Chem 259:9997-10003]. This was confirmed by the observation that, although it inhibited respiration, AOA did not affect the efflux of citrate from the mitochondria. Thus citrate does not appear to be a cycle component and is directly transported to the medium. Therefore, it was concluded that the truncated TCA cycle in HeLa cells is the result of both a low rate of citrate synthesis and an active citrate transporter. DNP (10 microM) induced a state III-like respiration only in the presence of succinate, which supports the evidence that NAD-linked dehydrogenases were not coupled to respiration, and suggests that these mitochondria may have a defect in complex I of the electron transport chain. Arising from the present results with HeLa cells and results extant in the literature, it has been proposed that a major regulating mechanism for the flux of glutamate carbon in tumour cells is the competitive inhibition exerted by 2-oxoglutarate on aspartate and alanine aminotransferases. This has been discussed and applied to the data.
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PMID:Oxidation of glutamine in HeLa cells: role and control of truncated TCA cycles in tumour mitochondria. 944 77

A recombinant B. megaterium strain was used for the heterologous production of a glucosyltransferase (dextransucrase). To better understand the physiological and metabolic responses of the host cell to cultivation and induction conditions, proteomic analysis was carried out by combined use of two-dimensional gel electrophoresis and mass spectrometry (2-DE/MS) for protein separation and identification. 2-DE method was optimized for the separation of intracellular proteins. Since the genome of B. megaterium is not yet available, peptide sequencing using peptide fragment information obtained from nanoelectrospray ionization quadrupole-time-of-flight tandem mass spectrometry (ESI-QqTOF MS/MS) was applied for protein identification. 167 protein spots were identified as 149 individual proteins, including most enzymes involved in the central carbon metabolic pathways and many enzymes related to amino acid synthesis and protein synthesis. Based on the results a 2-DE reference map and a corresponding protein database were constructed for further proteomic approaches on B. megaterium. For the first time it became possible to perform comparative proteomic analysis on B. megaterium in a batch culture grown on glucose with xylose induction for dextrasucrase production. No significant differences were observed in the expression changes of enzymes of the glycolysis and TCA cycle, indicating that dextransucrase production, which amounted to only 2 % of the entire protein production, did not impose notable metabolic or energetic burdens on the central carbon metabolic pathway of the cells. However, a short-term up-regulation of aspartate aminotransferase, an enzyme closely related to dextransucrase production, in the induced culture demonstrated the feasibility to use 2-DE method for monitoring dextransucrase production. It was also observed that under the cultivation conditions used in this study B. megaterium tended to channel acetyl-CoA into pathways of polyhydroxybutyrate production. No expression increases were found with cytosolic chaperones such as GroEL and DnaK during dextransucrase production and secretion, whereas a strong up-regulation of the oligopeptide-binding protein OppA was observed in correlation with an increased secretion of dextransucrase into the culture medium.
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PMID:Proteome analysis of a recombinant Bacillus megaterium strain during heterologous production of a glucosyltransferase. 1592 46

Disease caused by viruses, especially white spot syndrome virus (WSSV), present the greatest challenge to shrimp aquaculture worldwide. Massive tissue disintegration occurs in WSSV-infected ectodermal and mesodermal tissues of penaeid shrimp. The activities of membrane bound phosphatases (Na(+)K(+)ATPase, Ca(2+)ATPase, Mg(2+)ATPase and Total ATPase), transaminases (alanine transaminase (ALT) and aspartate transaminase (AST)) and mitochondrial enzymes (isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), alpha-ketoglutarate dehydrogenase (KGDH), NADH dehydrogenase, cytochrome C oxidase) in WSSV-infected tissues (hemolymph, hepatopancreas, gills and muscle) of Fenneropenaeus indicus were determined at intervals after WSSV infection (0, 24, 48, 72 and after 72 h (moribund)). The activities of phosphatases, transaminases and mitochondrial enzymes in healthy as compared with WSSV-infected hemolymph, hepatopancreas, gills and muscle showed marked divergence throughout the course of infection. WSSV infected hemolymph, hepatopancreas, gills and muscle exhibited significantly reduced activity of membrane bound phosphatases compared with the uninfected animals. Inactivation of these enzymes may occur due to increased production of free radicals, that cause conformational change by oxidation of 'SH' groups present at the active site. Significantly marked elevation in the activities of transaminases (ALT and AST) was observed in WSSV-infected hemolymph, hepatopancreas, gills and muscle compared to the uninfected tissues. This may be due to leakage of these enzymes from the damaged tissues. The activities of mitochondrial enzymes in WSSV-infected tissues were significantly decreased compared to the activities in uninfected animals. WSSV-infected animals showed reduced feeding that may have led to decreased oxidation of glucose via the TCA cycle. Excessive production of free radicals in WSSV-infected animals may have affected aerobic oxidation leading to lower production of ATP. It is concluded that membrane dynamics play a major role in the pathogenesis of WSSV infection.
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PMID:Activities of membrane bound phosphatases, transaminases and mitochondrial enzymes in white spot syndrome virus infected tissues of Fenneropenaeus indicus. 1641 26

Vibrio parahaemolyticus ATCC 27519 was chosen as indicator of aquacultural pathogenic bacteria to determine the antibacterial activity and mechanism of copper-bearing montmorillonite (Cu-MMT) in vitro. The results indicated that montmorillonite (MMT) had no antibacterial activity. The minimum inhibitory concentration (MIC) and bactericidal concentration (MBC) of Cu-MMT on Vibrio parahaemolyticus were 75 and 300 mg/L, respectively. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) of bacteria were examined and the results showed treatment with Cu-MMT could lead to significant release of intracellular enzymes from the tested bacteria suggesting that the permeability of the cell membrane increased and bacteria suffered injury. Three typical inhibitors (malonic acid, iodine acetic acid and phosphate sodium) were used to further study the inhibitory pathways of respiratory metabolism. Cu-MMT effectively inhibited respiratory metabolism of Vibrio parahaemolyticus, with the respiratory inhibition percent (I(R)) of 31.8%. The respiratory superposing inhibition percent after addition of phosphate sodium, iodine acetic acid and malonic acid was 48.6%, 27.8% and 17.5%, respectively. These results indicated that the effect of malonic acid on superposing inhibition percent of Cu-MMT for bacteria is the lowest; thus, the synergic action between Cu-MMT and malonic acid is the weakest, indicating that they inhibited the same pathway of respiratory metabolism, i.e. the TCA pathway, which is the most important pathway of carbohydrate metabolism. The atomic force microscope image of Vibrio parahaemolyticus exposed to Cu-MMT showed that Cu-MMT could rupture the bacterial cell membrane.
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PMID:[Study on the antibacterial mechanisms of copper-bearing montmorillonite]. 1693 15

This study was designed to investigate the protective effects of two traditionally used Turkish medicinal plants, Camellia sinensis (CS) and Urtica dioica L. (UD), beverages used against chemical carcinogen trichloroacetic acid (TCA)-exposure in rats. The preventive potential of the plant infusions was evaluated by measuring the level of serum marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK), acid phosphatase (ACP), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH); antioxidant defense systems, reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT); and lipid peroxidation (malondialdehyde, MDA) content in various organs of rats. Twenty four healthy rats were randomly allotted into four experimental groups: A (untreated control), B (only TCA-treated), C (TCA+CS treated) and D (TCA+UD treated). At the end of the 50 days, the plant infusions possessed chemoprotective effects, deduced by the remaining TCA-induced increased serum damage marker enzyme, lipid peroxidation and antioxidative system in rats compared with those of the control and TCA-exposed rats. According to the results, while the levels of AST, ALT and CPK increased in group B, no significant changes were observed in groups C and D. The MDA content slightly increased in tissues of all groups, being higher in group B. Antioxidant enzyme activities such as SOD and CAT increased significantly in the brain, liver and kidney of group B while they did not change significantly except for in the kidney in groups C and D. The GSH level and the ancillary enzyme GR activity did not change significantly in organs of all groups. On the other hand, the drug metabolizing enzyme, GST, activity decreased significantly in the brain, liver and kidney of group D while slight changes were observed for the other groups. The results revealed that TCA exposure induced oxidative stress in rat tissues, however, in plant beverage supplemented groups, a significant protective effect of CS and UD against TCA-induced oxidative injury was recorded. Hence, the study revealed that the constituents present in CS and UD impart protection against carcinogenic chemical induced oxidative injury that may result in the development of cancer. Also the observations, along with changes, suggest that both CS and UD may possess preventive potential during a 50-day protective exposure.
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PMID:Elevation protective role of Camellia sinensis and Urtica dioica infusion against trichloroacetic acid-exposed in rats. 1762 76

Today's world is increasingly seeking ways to replace the synthetic drugs with the therapeutic power of natural products. This study was designed to investigate the protective effects of Foeniculum vulgare (FV) and Salvia officinalis (SO) waters infusions against carcinogen chemical trichloroacetic acid (TCA)-exposure in rats. The chemopreventive potential of the plant infusions were evaluated by measuring levels of serum marker enzymes [aspartate aminotransferase (AST), alanin aminotransferase (ALT), creatine phosphokinase (CPK), acid phosphatase (ACP), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)], antioxidant defense systems [Reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)] and lipid peroxidation level (Malondialdehyde = MDA) in various tissues of rats. Female Sprague-Dawley rats, weighing 150-200 g, were randomly allotted into four experimental groups. While the control group (A) received only natural spring water, the treatment B group (0.2% TCA) supplied with the drinking water containing 0.2% TCA, the treatment C (TCA + FV infusion) and D (TCA + SO infusion) groups drank the drinking water containing 0.2% TCA and 2.5% the plant grains and leaves ad libitum for 50 days during experiment. At the end of the 50 days experiment, TCA and the plant's infusions caused different affect on the serum marker enzymes, tissues antioxidant defense systems and lipid peroxidation against TCA-exposed in rats with comparison to those of TCA exposed and control rats. According to the results, both TCA and TCA + plants infusions caused a significant increase in serum AST, ALT and CPK activity. Non-enzymic antioxidant GSH level significantly increased in the brain whereas reduced in the erythrocytes and kidney of TCA + FV and TCA + SO as compared to TCA group and control. While MDA content slightly increased in tissues of TCA group in comparison to those of control, significantly decreased in the brain, liver and kidney of rats of TCA + FV and TCA + SO groups as compared to TCA group and control. Antioxidative enzyme activity such as CAT and SOD significantly increased in the brain, liver and kidney tissues of TCA induced group whereas reduced the same enzymes activities as compared to TCA group. The ancillary enzyme GR activity significantly depleted in the brain and kidney of TCA + FV and TCA + SO groups in comparison to those of TCA exposed and control rats. In addition, the drug metabolizing enzyme GST activity significantly declined in the brain and kidney of TCA + FV and TCA + SO groups in comparison to those of TCA exposed and control rats, whereas, also reduced in the liver of TCA + FV and TCA + SO groups in comparison to those of TCA exposed rats. It was concluded that the levels of serum marker enzymes were found not to be decreased in plants treated groups due to hepatic damage induced by TCA. Also the four antioxidant enzymes were found to be activated in different degrees following TCA treatment and declined the activation of the enzymes the plant infusions accompanied by significant reduction in MDA concentration in the tissues. The observations, along with changes, might suggest that the both FV and SO may possess antioxidant properties during the period of a 50-day protective exposure.
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PMID:Determination of chemopreventive role of Foeniculum vulgare and Salvia officinalis infusion on trichloroacetic acid-induced increased serum marker enzymes lipid peroxidation and antioxidative defense systems in rats. 1799 40

Cytochrome P450 (CYP) 2E1 was suggested to be the major enzyme involved in trichloroethylene (TRI) metabolism and TRI-induced hepatotoxicity, although the latter molecular mechanism is not fully understood. The involvement of CYP2E1 in TRI-induced hepatotoxicity and its underlying molecular mechanism were studied by comparing hepatotoxicity in cyp2e1+/+ and cyp2e1-/- mice. The mice were exposed by inhalation to 0 (control), 1000, or 2000 ppm of TRI for 8 h a day, for 7 days, and TRI-hepatotoxicity was assessed by measuring plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histopathology. Urinary metabolites of trichloroethanol and trichloroacetic acid (TCA) were considerably greater in cyp2e1+/+ compared to cyp2e1-/- mice, suggesting that CYP2E1 is the major P450 involved in the formation of these metabolites. Consistent with elevated plasma ALT and AST activities, cyp2e1+/+ mice in the 2000 ppm group showed histopathological inflammation. TRI significantly upregulated PPARalpha, which might function to inhibit NFkappaB p50 and p65 signalling. In addition, TRI-induced NFkappaB p52 mRNA, and significantly positive correlation between NFkappaB p52 mRNA expression and plasma ALT activity levels were observed, suggesting the involvement of p52 in liver inflammation. Taken together, the current study directly demonstrates that CYP2E1 was the major P450 involved in the first step of the TRI metabolism, and the metabolites produced may have two opposing roles: one inducing hepatotoxicity and the other protecting against the toxicity. Intermediate metabolite(s) from TRI to chloral hydrate produced by CYP2E1-mediated oxidation may be involved in the former, and TCA in the latter.
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PMID:Molecular mechanism of trichloroethylene-induced hepatotoxicity mediated by CYP2E1. 1856 63

Trichloroethylene-induced hypersensitivity dermatitis is one of the serious occupational health events in China, however, little is known about the clinical features and possible mechanism of this disorder. The objective of the present study was to report some typical trichloroethylene-induced dermatitis patients and investigate their occupational exposure as well as the clinical features. We sampled and tested some cleaning agents from the companies where TCE-induced skin disorder occurred, the trichloroethylene concentrations were also monitored in the workplace air. Additionally, the symptoms, signs and laboratory test results of patients were collected. TCE concentrations varied from 10.2% to 91.4% in the cleaning agent by gas chromatography-mass chromatography analysis, and TCE levels in the workplace air ranged between 18 mg/m(3) and 683 mg/m(3), at most sampled sites TCE levels were higher than China national health standard for TCE. The trichloroethylene exposure time of the patients was 5-90 days (average 38.2 d), the patients with headache, dizziness, skin itch, fever were 90.5%, 100%, 100%, and 61.9%, respectively. 85.7% patients had skin erythema, 90.5% with rashes, and 38.1% with blisters. In addition, liver enlargement occurred in 3 patients, the abnormal rate of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (T-Bil) were 90.5%, 85.7% and 76.2%, respectively. 6 out of 15 patients were with abnormal electrocardiogram, and trichloroacetic acid (TCA) elevated in 14 patients (66.7%). Taken together, the major detrimental effect of trichloroethylene was to induce hypersensitivity dermatitis and liver dysfunction, the occurrence of this disorder is likely related to the individual hypersensitivity to trichloroethylene exposure.
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PMID:Severe hypersensitivity dermatitis and liver dysfunction induced by occupational exposure to trichloroethylene. 1936 38

Legionella pneumophila is an aquatic bacterium that is also the agent of Legionnaires' disease pneumonia. Since L. pneumophila is transmitted directly from the environment to the lung, it is important to understand how legionellae survive at low temperatures. To identify genes that are needed for L. pneumophila growth at low temperature, we screened a population of mutagenized legionellae for strains that are specifically impaired for growth at 17 degrees C. From the 7,400 mutants tested, 11 displayed defects ranging from ca. 10-fold to a complete inability to grow at the low temperature. PCR and sequence analysis were then utilized to identify the genes whose loss had compromised growth. The proteins thereby implicated in low-temperature growth included components of the type II secretion system (LspE, LspG, LspH), a lipid A biosynthetic enzyme (LpxP), a ribonuclease (RNAse R), an RNA helicase (CsdA/DeaD), TCA cycle enzymes (citrate synthase), enzymes linked to fatty acid (FadB) or amino acid (aspartate aminotransferase) catabolism, and two putative membrane proteins that were, based upon their sequences, unlike previously characterized proteins. Given the magnitude of their mutant's defect, the aspartate aminotransferase, RNA helicase, and one of the putative membrane proteins were the factors most critical for L. pneumophila low-temperature growth. Thus, L. pneumophila not only employs some of the same processes and factors as other bacteria do in order to survive at low temperatures (e.g., LpxP, CsdA), but it also appears to possess novel modes of cold adaptation.
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PMID:Mediators of lipid A modification, RNA degradation, and central intermediary metabolism facilitate the growth of Legionella pneumophila at low temperatures. 1976 2

Gfi-1 is a crucial transcriptional repressor for the precise regulation of cell proliferation and differentiation in hematopoiesis. Recently, this protein has also been demonstrated to be capable of restricting the proliferation of hematopoietic stem cells, a process that appears to be vital for the long-term competency of hematopoietic stem cells. These two seemingly opposite outcomes of regulation are likely to arise from its interactions with a variety of cellular partners. Such interactions can directly affect the genes that Gfi-1 recognizes through its DNA binding zinc-finger domain. In this work, we report the determination of the solution structure of Gfi-1 zinc fingers 3-5 in complex with a 16-mer consensus DNA using multidimensional NMR method. Unlike a proposed minor-groove binding model based on methylation interference experiments, our structure clearly shows that Gfi-1 zinc fingers 3-5 bind into the major groove of the target DNA reminiscent of canonical C(2)H(2) zinc-finger domains. The fourth and fifth zinc fingers recognize the AATC core sequence by forming base-specific hydrogen bonds between the side chains of Asn382, Gln379, and Asp354 and the bases of the invariant adenines and cytosine. Overall, the current work provides valuable insight into the structural determinants for DNA binding specificity, in particular for the TCA triplet that has not been observed in any other structures of zinc finger-DNA complexes, as well as molecular rationales for a naturally occurring mutation that causes acute myeloid leukemia.
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PMID:Solution structure of Gfi-1 zinc domain bound to consensus DNA. 2015 36


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