Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The retina of honeybee drone is a nervous tissue with a crystal-like structure in which glial cells and photoreceptor neurons constitute two distinct metabolic compartments. The phosphorylation of glucose and its subsequent incorporation into glycogen occur in glia, whereas O2 consumption (QO2) occurs in the photoreceptors. Experimental evidence showed that glia phosphorylate glucose and supply the photoreceptors with metabolic substrates. We aimed to identify these transferred substrates. Using ion-exchange and reversed-phase HPLC and gas chromatography-mass spectrometry, we demonstrated that more than 50% of 14C(U)-glucose entering the glia is transformed to alanine by transamination of pyruvate with glutamate. In the absence of extracellular glucose, glycogen is used to make alanine; thus, its pool size in isolated retinas is maintained stable or even increased. Our model proposes that the formation of alanine occurs in the glia, thereby maintaining the redox potential of this cell and contributing to NH3 homeostasis. Alanine is released into the extracellular space and is then transported into photoreceptors using an Na(+)-dependent transport system. Purified suspensions of photoreceptors have similar alanine aminotransferase activity as glial cells and transform 14C-alanine to glutamate, aspartate, and CO2. Therefore, the alanine entering photoreceptors is transaminated to pyruvate, which in turn enters the Krebs cycle. Proline also supplies the Krebs cycle by making glutamate and, in turn, the intermediate alpha-ketoglutarate. Light stimulation caused a 200% increase of QO2 and a 50% decrease of proline and of glutamate. Also, the production of 14CO2 from 14C-proline was increased. The use of these amino acids would sustain about half of the light-induced delta QO2, the other half being sustained by glycogen via alanine formation. The use of proline meets a necessary anaplerotic function in the Krebs cycle, but implies high NH3 production. The results showed that alanine formation fixes NH3 at a rate exceeding glutamine formation. This is consistent with the rise of a glial pool of alanine upon photostimulation. In conclusion, the results strongly support a nutritive function for glia.
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PMID:Glial cells transform glucose to alanine, which fuels the neurons in the honeybee retina. 812 Jun 29

An inverse relation is known to link blood potassium with renal synthesis and the release of ammonia. Given the liability of hyperammonemia for precipitating hepatic encephalopathy (HE), 28 patients affected by stage I HE were equally divided into two groups and maintained up to their death at the highest (5.4-5.5 mEq/l) or the lowest (3.5-3.6 mEq/l) normokalemia levels. When compared with the lowest normokalemia group, the highest one showed an early, albeit transient, improvement in the mental state (as assessed by both EEG and psychiatric investigations) and to a lesser extent in hepatic functions (as assessed by the variations in serum bilirubin, GPT, GGT and plasma prothrombin time). In the highest normokalemia group the survival was also prolonged. The cause of this improvement may be related to the induced decrease in blood pH, the consequent depression of renal ammoniagenesis and the rise in the arterial and urine NH+4/NH3 ratios. These factors reduce the entry of ammonia into the cells and enhance the urinary excretion of this metabolite, respectively.
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PMID:The importance of the highest normokalemia in the treatment of early hepatic encephalopathy. 816 17

Fulminant hepatic failure (FHF) is a poorly understood condition in which total liver failure occurs and is thought to be caused by a variety of conditions including Reye's syndrome, hepatitis, drug overdoses, and vascular insufficiency. While this condition is an uncommon one, it carries with it a high fatality rate and must therefore be diagnosed as rapidly as possible. Six patients have been observed over a two-year period with biopsy and/or autopsy-confirmed FHF: one with acute hepatitis B-delta; three with histories of alcoholism, two of them with cirrhosis; one with acute tylenol overdose; and one with hepatic vascular insufficiency. All of these patients, except one, exhibited a rapid, fatal downhill course after onset of symptoms. In all of these patients, a consistent elevation was observed in serum levels of aspartate aminotransferase (AST) or serum glutamate oxaloacetate transaminase (SGOT) and alanine aminotransferase (ALT) or serum glutamate pyruvate transaminase (SGPT) such that the ratio of AST to ALT was significantly greater than 1 and in serum levels of ammonia. Other liver function tests were found to be abnormal but not in so consistent a pattern, although total protein and albumin were found to be significantly decreased in all of these patients. The stereotypical elevation of the transaminases with high AST-to-ALT ratios and the rise in ammonia appear to characterize this life-threatening illness most reliably.
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PMID:Serum analyte pattern characteristic of fulminant hepatic failure. 820 19

Idiopathic hepatic fibrosis was diagnosed by liver biopsy in 15 young dogs, of which nine were German shepherds. Clinical signs included ascites, anorexia, weight loss and hepatic encephalopathy. Erythrocyte microcytosis was a consistent clinical feature, and clinical chemistry generally revealed hypoproteinaemia and high serum activities of alkaline phosphatase and, to a smaller extent, alanine aminotransferase. Fasting blood ammonia and serum bile acid concentrations were increased in most dogs examined, and all the dogs tested had prolonged retention of sulfobromophthalein at 30 minutes. Multiple acquired portosystemic shunts were revealed by laparotomy and/or portography. Non-inflammatory fibrosis was present to different degrees in all the dogs' livers, and on the basis of its predominant location these were classified as having central perivenous fibrosis, diffuse pericellular fibrosis or periportal fibrosis. The response to symptomatic treatment and anti-fibrotic therapy with glucocorticosteroids or colchicine was variable. Seven dogs died or were euthanased shortly after diagnosis, but one dog survived two-and-a-half years, and three dogs were still alive more than four years after the initial diagnosis.
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PMID:Idiopathic hepatic fibrosis in 15 dogs. 821 1

The number of clinical liver transplants that can be performed is limited by the availability of suitable donor organs. If it were possible to harvest and use livers after cardiac arrest, the supply could be improved. The mechanisms of damage in warm ischemia are not yet well understood and the consequences of transplanting a liver that is unable to provide immediate life-support are unacceptable. This study aims to identify areas for more detailed study in an attempt to improve the quality of livers harvested after significant warm ischemia, and to select acceptable organs for transplantation. Porcine livers were subjected to 75 min of warm ischemia and then perfused at 37 degrees C for 3 hr, during which period biochemical monitoring was carried out. At the end of the perfusion, histological and transmission electron microscopical studies were made. Large amounts of the intracellular enzymes ALT, AST, and LDH were released into the perfusate during the first 30 min of perfusion, but this--and the further amounts released during the subsequent 2.5 hr--was influenced by the composition of the perfusate. The inclusion of the substrates fructose and oleate, plus amino acids, substantially reduced this release and also improved the ability of the livers to metabolize ammonia. Oxygen free-radical scavengers had a significant, but smaller, beneficial effect. Electron microscopy confirmed the value of perfusion in improving cell morphology, and the additional value of including metabolic substrates. This study shows that hepatocellular structure and function can be improved by appropriate perfusion methods that also provide a simple means of monitoring some important functions. Both metabolic support and neutralization of oxygen free-radical action have a role to play in this approach to rendering ischemically injured livers acceptable for clinical use.
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PMID:The possibility of resuscitating livers after warm ischemic injury. 833 57

Recent experience suggests that a diagnosis of Reye's syndrome based on clinical and biochemical grounds alone may be unreliable. Two patients are presented here, whose clinical manifestation suggested Reye's syndrome. The biochemistry data were also compatible with Reye's syndrome except that the levels of serum AST and ALT were significantly higher with normal serum ammonia level. Blood amino acid and urinary organic acid assay all showed negative findings. Histological findings of the liver showed marked centrilobular necrosis rather than fatty metamorphosis. The muscle biopsies did not show lipid accumulation in the muscle fibers as well. The findings in our patients suggested that a confirmatory diagnosis of Reye's syndrome requires a characteristic pathological findings of the liver in order to differentiate Reye's syndrome from Reye-like syndrome, especially acute encephalopathy associated with centrilobular necrosis of the liver.
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PMID:[Acute encephalopathy associated with centrilobular necrosis of liver mimicking Reye's syndrome--report of two cases]. 838 58

An investigation on the relative presence of some protein metabolic enzymes, namely aspartate aminotransferase (AST), alanine aminotransferase (ALT), NAD+ and NADP+ dependent glutamate dehydrogenase (GLDH) and arginase in cyst wall (CW), cyst fluid (CF) and zoite (ZT) fractions of the sarcocysts of Sarcocystis fusiformis in the oesophageal muscles of Indian water buffalo was carried out. Both the transaminases were present in all the fractions of the cyst, although in variable amounts. There was a higher level of AST activity than of ALT activity. AST activity was the highest in ZT, whereas ALT activity was at a maximum in the CF fraction. The levels of activity of NAD+ and NADP+ dependent GLDH and arginase remained beyond detectable limits. The study revealed that the intermediates of carbohydrate metabolism are linked to protein metabolism by transaminases. The possibility of concomitant removal of ammonia and its subsequent incorporation into the urea cycle is ruled out in this parasitic protozoan.
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PMID:Sarcocystis fusiformis: some protein metabolic enzymes in various fractions of sarcocysts of buffalo (Bubalus bubalis). 844 61

Thermococcus profundus, a hyperthermophilic archaeon, did not exhibit detectable glutamine synthetase activity, although the organism possessed an extraordinarily high level of glutamate dehydrogenase (GDH), the content of which reached over 10% of total soluble proteins. This GDH was purified to homogeneity. The enzyme had a molecular weight of 263,000 and was composed of six homogeneous subunits of molecular weight 43,000. The enzyme was extremely thermostable with a half life of 1 h at 90 degrees C. Circular dichroism (CD) spectra of the enzyme revealed gradual unfolding of alpha-helices upon exposure to increasing temperature. The enzyme reaction was strongly biased toward glutamate formation. T. profundus excreted L-alanine into the medium, and the concentration reached mM. High activity of alanine aminotransferase (AAT) was present in the cells, while no alanine dehydrogenase activity was detected. The alanine formation may be initiated by ammonia uptake by GDH followed by aminotransfer from glutamate to pyruvate by AAT.
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PMID:Properties of glutamate dehydrogenase and its involvement in alanine production in a hyperthermophilic archaeon, Thermococcus profundus. 869 Jul 22

Oxygen free radicals have been shown to be implicated in ischemic tissue injury, and free radical-induced reactions may also play an important role in the pathophysiology of circulatory shock. The present study was designed to investigate the potential use of ascorbic acid as an exogenous antioxidant on the liver's recovery from hemorrhagic shock in situ. Rats (fasted overnight) were subjected to 60 min of hemorrhagic shock (HS) (mean arterial pressure = 40 mmHg) under pentobarbital anesthesia, followed by retransfusion of the shed blood. One-half of the animals (n = 6) were injected with 10 mg/kg of ascorbic acid prior to induction of shock, while untreated animals (n = 6) received the same volume of saline solution. in untreated animals, systemic plasma levels of malondialdehyde rose from 1.07 +/- .08 during normotension (NT) to 1.36 +/- .18* 60 min after resuscitation (RS), documenting oxygen free radical-induced lipid peroxidation. Accordingly, plasma levels of alanine aminotransferase (16.5 +/- 2.5; 34.9 +/- 12.3*; 105.8 +/- 68.7* U/L; NT/HS/RS) and ammonia (127 +/- 40; 532 +/- 160*; 304 +/- 244* micrograms/dL) rose significantly during the experiment. Hepatic ATP content of the liver fell from 4.8 +/- .83 to .56 +/- .27* after HS and recovered partially to 2.7 +/- 1.6* mumol/g after RS. Leukocyte infiltration in the liver, indicated by tissue levels of myeloperoxidase, remained constant during HS but rose during RS (37.9 +/- 18.5; 38.6 +/- 16.4; 81.4 +/- 30.7*, arbitrary units), thus documenting an inflammatory reaction after HS. In the ascorbic acid group, plasma levels of malondialdehyde were comparable to those of untreated animals after RS, as were enzyme concentrations and ammonia. No differences were observed with regard to the tissue concentrations of ATP or myeloperoxidase. Mean arterial blood pressure as well as liver tissue perfusion, as measured by Laser Doppler flowmetry, did not show significant differences between the groups. It was concluded that, although an effect of oxygen free radicals on liver tissue could be found during and after HS, treatment with ascorbic acid alone, in our model, failed to ameliorate the recovery of the animals upon resuscitation (values are mean +/- SD; *, p < .05 vs. NT; one-way ANOVA).
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PMID:No evidence for a protective effect of ascorbic acid on free radical generation and liver injury after hemorrhagic shock in rats. 872 88

Freshwater fish, Cyprinus carpio, was exposed to sublethal concentration (3 microg liter-1) of cypermethrin for 5 and 10 days to examine the changes in the transamination process during the formation of nitrogenous end products in four functionally different tissues, namely, gill, liver, brain, and muscle. Increases in total and soluble protein contents were noticed in all the tissues of exposed fish with a decrease in free amino acids and protease activity. Activity levels of both the transaminases, aspartate aminotransferase and alanine aminotransferase, and glutamate dehydrogenase were elevated, indicating active transamination and oxidative deamination. Attenuation of ammonia was consistent in both treatment groups. However, urea level decreased at the 5-day exposure period but increased by Day 10, manifesting the conversion of toxic ammonia to urea. Glutamine content was consistently raised upon exposure to the toxicant. In support of this, increases in glutamine synthetase and suppression of glutaminase were noticed. It clearly indicates that ammonia is not stored in the tissues in spite of active oxidative deamination when the fish is in a polluted environment. All the observations made demonstrate that the fish has adopted more than one compensatory mechanism during the process of transamination of nitrogenous products.
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PMID:Action of cypermethrin on tissue transamination during nitrogen metabolism in Cyprinus carpio. 881 84


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