Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein hydrolysate-containing parenteral solutions have been reported to be hepatotoxic. Ten infants who were treated with a 20 percent glucose solution containing either 2.5 percent or 3.25 percent protein hydrolysate are reviewed. Their gestational ages were 30 to 40 weeks and births weights 1000 to 35000 g. Serum glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), leucine amino peptidase (LAP) and bilirubin were measured serially. Serum amino acids were measured and consistently demonstrated decreased levels of isoleucine and increased aspartic acid, glutamic acid, serine, proline, glycine, alanine, threonine and lysine. The amino acid imbalances were associated with transaminase elevations in eight infants. Serum bilirubin levels increased in six patients and LAP in four. Liver biopsies from three patients showed minimal to moderate hepatic parenchymal disease with cholestasis.
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PMID:The hepatotoxicity of parenteral protein hydrolysate-containing solutions. 82 62

The only exogenous substrates oxidized by mitochondria isolated from the flight muscle of the Japanese beetle (Popillia japonica) are proline, pyruvate and glycerol 3-phosphate. The highest rate of oxygen consumption is obtained with proline. The oxidation of proline leads to the production of more NH3 than alanine, indicating a functioning glutamate dehydrogenase (EC 1.4.1.2). Studies of mitochondrial extracts confirm the presence of a very active glutamate dehydrogenase, and this enzyme is found to be activated by ADP and inhibited by ATP. These extracts also show high alanine aminotransferase activity (EC 2.6.1.2) and a uniquely active "malic' enzyme (EC 1.1.1.39). The "malic' enzyme is activated by succinate and inhibited by ATP and by pyruvate. It is suggested that the input of tricarboxylate-cycle intermediate from proline oxidation is balanced by the formation of pyruvate from malate, and the complete oxidation of the majority of the pyruvate. Studies of the steady-state concentrations of mitochondrial CoASH and CoA thioesters during proline oxidation show a high succinyl (3-carboxypropionyl)-CoA content which falls on activating respiration with ADP. There is a concomitant rise in CoASH. However, the reverse transition, from state-3 to state-4 respiration, causes only very slight changes in acylation. The reasons for this are discussed. Studies of the mitochondrial content of glutamate, 2-oxoglutarate, malate, pyruvate, citrate and isocitrate during the same phases of proline oxidation give results consistent with control at the level of glutamate dehydrogenase and isocitrate dehydrogenase during proline oxidation, with the possibility of further control at "malic' enzyme. During the oxidation of pyruvate all of the tricarboxylate-cycle intermediates and NAD(P)H follow the pattern of changes described in the blowfly (Johnson & Hansford, 1975; Hansford, 1974) and isocitrate dehydrogenase is identified as the primary site of control.?2OAuthor
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PMID:The nature and control of the tricarboxylate cycle in beetle flight muscle. 120 Sep 85

Evidence is provided for the utilization of glutamine by calvaria and compact bone of rat. Glutamine was actively transported into calvaria, principally by sodium-dependent mechanisms; its uptake was significantly inhibited by neutral amino acids (alanine, proline, serine, asparagine) and glutamine analogs (L-glutamate-gamma-hydroxamate, albizziin). Glutamine was degraded to ammonia and glutamate by phosphate-dependent glutaminase, a mitochondrial enzyme present in both calvaria and compact bone. The enzyme exhibited an apparent Kmgln of 2.35 mM, a KactPO4 of 25 mM, and a broad pH optimum (7.5-9.5). It was inactivated by incubation of intact calvaria or bone homogenates with the glutamine analogs 6-diazo-5-oxo-L-norleucine (DON) and a 2-amino-4-oxo-5-chloropentanoic acid (chloroketone). Such treatment also severely inhibited (greater than 95%) both ammonia and 14CO2 formation from [U-14C]glutamine. Glutamate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities were measured in bone. Amino-oxyacetate, an aminotransferase inhibitor, inhibited 14CO2 formation from [U-14C]glutamine. The data indicate that glutamine can serve as a precursor of ammonia, glutamate, other amino acids (alanine, aspartate, ornithine, proline) and carbon dioxide in bone and that phosphate-dependent glutaminase, transaminases, and citric acid cycle activity contribute to the observed metabolism.
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PMID:Glutamine metabolism in bone. 613 80

Some experimental and clinical studies were done from the metabolic viewpoint to elucidate the characteristics of myonephropathic-metabolic syndrome. In experimental dogs with their femoral arteries ligated and two third of femoral muscles divided, aldolase and myoglobin showed remarkable increase without significant changes in electrolytes. Slight increase of GPT and GOT was observed. Amino acids showed elevation in urea, taurin, leucin, isoleucin, valine, threonine, 3-methylhistidine, phenylalanine, histidine, lysine, methionine, tyrosine and anserin and decrease in glutamine, alanine, glycine, proline, carnosine, citrullin and arginine. In patients with acute arterial occlusion, potassium, GOT, LDH, CPK, lactate and pyruvate increased moderately and myoglobin showed remarkable increase and aldolase slight increase. Amino acids showed remarkable increase in 3-methylhistidine and beta-amino-isobutyric acid and moderate increase in phenylalanine and arginine. These results revealed that measurement of free amino acid concentration, especially that of methylhistidine as well as myoglobin, pyruvate, lactate and some other enzymes might be of great help to predict the prognosis of patients with acute arterial occlusion of the extremities.
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PMID:[Metabolic study on acute arterial occlusion of the extremities]. 667 89

Neutral amino acid transport was investigated in Leishmania promastigotes. Proline and alanine transport occur against their concentration gradient although there is a very rapid (40% at 30 min) conversion of proline to alanine. Uptake of these amino acids occurs by a sodium-independent route which is completely eliminated by addition of CCCP or KCN. Km values for proline and alanine are 80 microM and 63 microM with Vmax values of 6.4 and 7.2 nmol/min per mg dry weight, respectively. Countertransport of proline, alanine and phenylalanine was measured by loading the cells with a variety of neutral amino acids and proline analogs, followed by CCCP addition. The effect of aminooxyacetic acid, an inhibitor of alanine aminotransferase (EC 2.6.1.2), on proline and alanine countertransport was also examined. The results obtained are consistent with the presence of at least two systems for neutral amino acid transport in Leishmania promastigotes.
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PMID:Neutral amino acid transport in Leishmania promastigotes. 684 19

In order to regulate cell volume during hyperosmotic stress, the intertidal copepod Tigriopus californicus, like other aquatic crustaceans, rapidly accumulates high levels of intracellular alanine, proline, and glycine. Glutamate-pyruvate transaminase (GPT; EC 2.6.1.2), which catalyzes the final step of alanine synthesis, is genetically polymorphic in T. californicus populations at Santa Cruz, California. Spectrophotometric studies of homogenates derived from a homozygous isofemale line of each of the two common GPT alleles indicated that the GPTF allozyme has a significantly higher specific activity than the GPTS allozyme. Under conditions of hyperosmotic stress, individual adult copepods of GPTF and GPTF/S genotypes accumulated alanine, but not glycine or proline, more rapidly than GPTS homozygotes. When young larvae were subjected to the same hyperosmotic conditions, GPTS larvae suffered a significantly higher mortality than GPTF or GPTF/S larvae. These results suggest that the biochemical differences among GPT allozymes result in specific physiological variation among GPT genotypes and that this physiological variation is manifested in differential genotypic survivorships under some naturally occurring environmental conditions.
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PMID:Physiological effects of an allozyme polymorphism: glutamate-pyruvate transaminase and response to hyperosmotic stress in the copepod Tigriopus californicus. 686 Feb 93

The amphistomes Gigantocotyle explanatum and Gastrothylax crumenifer utilize leucine, alanine, proline and methionine during in vitro incubations. Autoradiography on sections of these flukes reveal a time-dependent differential incorporation of tritium-labelled amino acids in various tissues. The tegument appears to be the primary surface through which amino acids are absorbed. Following absorption, the reappearance of [3H]-leucine and [3H]-alanine on the tegumental surface during late chase periods indicates their possible involvement in tegumental secretion. A combination of diffusion and carrier-mediated uptake, possibly involving gamma-glutamyl transpeptidase, is indicated. The transport loci show differences in carrier-affinity (Kt) and maximum uptake velocities (Vmax) for amino acids under study, which suggest multiple transport molecules. Metabolic studies reveal that aspartate, alanine, ornithine, proline, leucine and methionine undergo transamination through 2-oxoglutarate-linked transaminases, distributed in the cytosolic and mitochondrial fractions of G. explanatum and G. crumenifer. With the exception of alanine transaminase, the enzyme levels in the cytosolic fraction were higher than the mitochondrial fraction of the two amphistomes. Predominantly cytosolic glutamate dehydrogenase which was comparatively higher in G. explanatum, catalyse amination of alpha-ketoglutarate. A high level of cytosolic arginase alone does not indicate a functional urea cycle. A tentative pathway of amino acid metabolism in these amphistomes is proposed.
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PMID:[3H]-amino acid uptake and metabolic studies on Gigantocotyle explanatum and Gastrothylax crumenifer (Digenea: Paramphistomidae). 763 32

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

Chronic administration of carbon tetrachloride in liquid paraffin (1.7) ip; 0.15 ml, (20 doses) has been found to produce severe hepatotoxicity, as seen from the elevated levels of serum and liver glutamate-pyruvate transaminase, alkaline phosphatase and lipid peroxides. The chronic administration of carbon tetrachloride was also found to produce liver fibrosis as seen from pathological analysis as well as elevated liver-hydroxy proline. Oral administration of ellagic acid was found to significantly reduce the elevated levels of enzymes, lipid peroxide and liver hydroxy proline in these animals and rectified liver pathology. These results indicate that ellagic acid administration orally can circumvent the carbon tetrachloride toxicity and subsequent fibrosis.
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PMID:Inhibition of liver fibrosis by ellagic acid. 905 8

The effect of long-term 'corn peptide (CP)' ingestion on alcohol metabolism was investigated in stroke-prone spontaneously hypertensive rats (SHR-SP) with alcohol loading. Long-term CP ingestion in the EtOH/CP group did not significantly increase plasma GOT and GPT activities but markedly increased hepatic ADH and ALDH activities. Intragastric CP administration prior to a dose of 1.0 g/kg ethanol significantly lowered the blood ethanol concentration in SHR-SP which had been loaded with ethanol for a long time. Compared with non-loaded SHR-SP (control group), the rats loaded for a long time with ethanol (EtOH group) showed high concentrations of taurine, glycine and histidine in the plasma. The plasma threonine and proline concentrations were significantly elevated by long-term CP ingestion (EtOH/CP group), but the plasma alanine concentration was rather decreased. These results suggest that short- or long-term CP ingestion may enhance the alcohol metabolism within the body because of an increase in ADH and ALDH activities as well as the alleviation of alcohol-related hepatic injury.
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PMID:Effect of long-term 'corn peptide' ingestion on alcohol metabolism in stroke-prone spontaneously hypertensive rats with alcohol loading. 908 82


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