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)

Treatment of rat liver mitochondria with digitonin followed by differential centrifugation was used to resolve the intramitochondrial localization of both soluble and particulate enzymes. Rat liver mitochondria were separated into three fractions: inner membrane plus matrix, outer membrane, and a soluble fraction containing enzymes localized between the membranes plus some solublized outer membrane. Monoamine oxidase, kynurenine hydroxylase, and rotenone-insensitive NADH-cytochrome c reductase were found primarily in the outer membrane fraction. Succinate-cytochrome c reductase, succinate dehydrogenase, cytochrome oxidase, beta-hydroxybutyrate dehydrogenase, alpha-ketoglutarate dehydrogenase, lipoamide dehydrogenase, NAD- and NADH-isocitrate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase, and ornithine transcarbamoylase were found in the inner membrane-matrix fraction. Nucleoside diphosphokinase was found in both the outer membrane and soluble fractions; this suggests a dual localization. Adenylate kinase was found entirely in the soluble fraction and was released at a lower digitonin concentration than was the outer membrane; this suggests that this enzyme is localized between the two membranes. The inner membrane-matrix fraction was separated into inner membrane and matrix by treatment with the nonionic detergent Lubrol, and this separation was used as a basis for calculating the relative protein content of the mitochondrial components. The inner membrane-matrix fraction retained a high degree of morphological and biochemical integrity and exhibited a high respiratory rate and respiratory control when assayed in a sucrose-mannitol medium containing EDTA.
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PMID:Enzymatic properties of the inner and outer membranes of rat liver mitochondria. 569 70

Effects of norepinephrine on gluconeogenesis and ureogenesis from glutamine by hepatocytes from fasted rats were assessed. Comparisons were made to asparagine metabolism and to the effects of NH4Cl and dibutyryl cyclic AMP. With asparagine as substrate, aspartate content was very high but norepinephrine, dibutyryl cyclic AMP, or NH4Cl had little effect on gluconeogenesis or ureogenesis. Metabolism of asparagine could be greatly enhanced by the combination of oleate, ornithine, and NH4Cl. However, even under these conditions, asparatate content remained high, and norepinephrine and dibutyryl cyclic AMP had little influence on glucose or urea synthesis. With glutamine as substrate, aspartate content was much lower, but was greatly elevated by norepinephrine, dibutyryl cyclic AMP, or NH4Cl. Each of these effectors strongly stimulated glucose and urea formation from glutamine. NH4Cl stimulation was accompanied by an increased glutamate and decreased alpha-ketoglutarate content. This suggests the mechanism for NH4Cl stimulation is a near-equilibrium adjustment to ammonia by glutamate dehydrogenase and aspartate aminotransferase rather than a principal involvement of glutaminase. Although both norepinephrine and dibutyryl cyclic AMP lowered alpha-ketoglutarate to the same extent, norepinephrine more rapidly increased aspartate content and led to a smaller accumulation of glutamate than did dibutyryl cyclic AMP. Moreover, only norepinephrine led to a rapid increase in succinyl-CoA concentration. The catecholamine effect could not be explained by specific changes in cytosolic or mitochondrial redox states. The results suggest that alpha-ketoglutarate dehydrogenase is a site of catecholamine action in rat liver. Since purified alpha-ketoglutarate dehydrogenase is known to be Ca2+ stimulated and Ca2+ flux is involved in catecholamine action, these findings also suggest that mitochondrial Ca2+ is elevated by catecholamines.
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PMID:Glutamine metabolism of isolated rat hepatocytes. Evidence for catecholamine activation of alpha-ketoglutarate dehydrogenase. 609 58

Metabolism of the glutamate group of amino acids--glutamic acid, gamma-amino-butyric acid, glutamine, aspartic acid and alanine--was studied in the brain of rat as a function of age. The levels of glutamic acid, glutamine and aspartic acid decreased while those of gamma-aminobutyric acid, and alanine increased with age. The results on the activity of the twelve enzymes involved in the metabolism showed that five of them (glutamate dehydrogenase, glutamine synthase, gamma-aminobutyric acid transaminase, succinic semialdehyde dehydrogenase and NAD+-isocitrate dehydrogenase) decreased, while four of them (glutaminase, glutamotransferase, glutamic acid decarboxylase, and alpha-ketoglutarate dehydrogenase) increased. The other three enzymes (aspartate aminotransferase, alanine aminotransferase and NADP+-isocitrate dehydrogenase) did not show any significant change in activity. An age-related increase was seen in alpha-ketoglutarate and ammonia, the intermediates involved in the metabolism of these amino acids. The changes in the level of these amino acids are discussed in relation to the altered energy metabolism during aging.
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PMID:Metabolism of the glutamate group of amino acids in rat brain as a function of age. 614 62

Rat liver mitochondria, stored with the energy-linked functions preserved or in aging conditions, were used to assay the activity of various enzymes during five days. The preservation of energy-linked functions was monitored by the respiratory control coefficient. ATPase, cytochrome oxidase and NADH dehydrogenase showed increased activity when the energy-linked functions were preserved. In aging conditions, cytochrome oxidase, NADH dehydrogenase and ATPase showed decreased activity. The ATPase activity increased only when mitochondria were stored in the presence of inhibitors of the electron transport chain. The activity of NADH oxidase did not change, and succinate oxidase and succinate dehydrogenase showed a small decrease in their activity. The enzymes of the matrix, alpha-ketoglutarate dehydrogenase, malate dehydrogenase and aspartate aminotransferase showed little decrease in activity under either of the conditions of storage. The total protein content decreased slightly under both conditions of storage. These results show that the activity of the enzymes analysed was maintained at reasonable levels, when the energy-linked functions of isolated mitochondria were preserved.
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PMID:Studies on rat liver mitochondria: 4. Enzyme activities in mitochondria preserved at 0-4 degrees C. 646 13

Weiss et al. (Circ. Res. 70: 392-408, 1992) proposed a model of the citric acid cycle (CAC) in myocytes and a system of 17 differential equations that can be used to describe the changes over time in enrichment of carbons C-2 and C-4 of glutamate under conditions of metabolic steady state. They also proposed an empirical measure (KT) of flux through the CAC, which has been shown to be correlated to O2 consumption in rat hearts perfused with acetate or a mixture of glucose and acetate. We report a new method for estimation of the absolute rate of the flux through the CAC in heart (vTCA), without the numerical solution of differential equations. Unlike KT, our estimate is equal to the rate of flux catalyzed by the alpha-ketoglutarate dehydrogenase complex (vTCA), not merely correlated with it. We also estimate the rate of flux catalyzed by aspartate aminotransferase (vTA) and by NADP(+)-dependent malic enzyme (an anaplerotic reaction). The formula for vTCA during administration of [2-13C]acetate is as follows: vTCA = M[(C-2ssLC-4)/[C-4ss(LC-4-LC-2)]], where C-2ss and C-4ss represent steady-state fractional enrichment, LC-2 and LC-4 represent dominant rate constants of C-2 and C-4 of glutamate, respectively, and M is the sum of concentrations of aspartate, glutamate, and intermediates of the CAC. The assumptions underlying our formula are as follows: 1) metabolic steady state is maintained, 2) exchange of molecules between cytosolic and mitochondrial compartments is rapid, 3) 13C enters pools of the CAC only from acetyl CoA via citrate synthase, 4) [citrate]/[glutamate] < 1 + (vTCA/vTA), and 5) (m-[glutamate])/M < C-2ss/C-4ss.
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PMID:Estimation of TCA cycle flux, aminotransferase flux, and anaplerosis in heart: validation with syntactic model. 790 Jul 86

Activity of a number of enzymes participating in the processes of structure metabolism and dynamics of inclusion of 14C-aspartate in initial strain of Staphylococcus aureus sensitive to antibiotics and strains containing plasmids of resistance to various antibiotics have been comparatively studied. An increase in activity of fumarate-hydratase, acetyl-KoA-carboxylase, aspartate aminotransferase and well as true increases (by the rate of inclusion of 14C-aspartate in a number of strains containing plasmids) of resistance to antibiotics as compared to plasmid-less variant are shown. This evidence for strengthening of biosynthetic function of a cycle of tricarbonic acids and, allowing for extremely low activity of alpha-ketoglutarate dehydrogenase, one can suppose that an open cycle of tricarbonic acids functions in the given strain of staphylococcus. The increase of the level of acetyl-KoA-carboxylase activity evidences for the intensification of lipid synthesis in antibiotic-resistant staphylococci as compared to the sensitive variants.
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PMID:[The activity of a number of anabolic metabolism enzymes in Staphylococcus aureus strains containing plasmids of antibiotic resistance]. 917 63

The effect of various metabolic inhibitors on the rate of oxygen consumption by procyclic culture forms of Trypanosoma congolense utilizing proline as substrate was investigated. Cyanide inhibited the rate of oxygen consumption by 81.0 +/- 6.7%, malonate inhibited the rate by 51.6 +/- 1.6% and Antimycin A by 73.1 +/- 5.9%. A combination of cyanide and malonate inhibited the rate of oxygen consumption by 84.9 +/- 6.7% while a combination of antimycin A and malonate inhibited the rate by 81.6 +/- 7.6%. Rotenone had no effect on the rate of respiration except when the intact cells were first permeabilized by digitonin after which rotenone decreased the rate of respiration by 20-30%. Salicylhydroxamate (SHAM) did not have any effect on the rate of oxygen consumption. Enzymes involved in the catabolism of proline with high activities were: proline dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase, NADP-linked malic enzyme, alanine aminotransferase and malate dehydrogenase. Activities of 1-pyrroline-5 carboxylate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase and NAD-linked malic enzyme were detectable but lower. The end products of proline catabolism were alanine and glutamate. Unlike the case in Trypanosoma brucei brucei aspartate was not detected. Possible pathways of proline catabolism in procyclic culture forms of T. congolense and of electron transfer are proposed.
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PMID:Catabolism of proline by procyclic culture forms of Trypanosoma congolense. 1042 13

Five synthetic, conformationally restricted alpha-ketoglutarate analogues were tested as substrates of a variety of dehydrogenases and aminotransferases. The compounds were found not to be detectable substrates of glutamate dehydrogenase, L-leucine dehydrogenase, L-phenylalanine dehydrogenase, lactate dehydrogenase, malate dehydrogenase, glutamine transaminase K, aspartate aminotransferase, alanine aminotransferase, and alpha-ketoglutarate dehydrogenase complex. However, two thermostable aminotransferases were identified that catalyze transamination between several L-amino acids (e.g., phenylalanine, glutamate) and the alpha-ketoglutarate analogues of interest. Transamination between L-glutamate (or L-phenylalanine) and the alpha-ketoglutarate analogues was found to be 0.13 to 1.08 micromol/h/mg at 45 degrees C. The products resulting from transamination between L-phenylalanine and the alpha-ketoglutarate analogues were separated by reverse-phase HPLC, and the newly formed amino acid analogues were analyzed by LC-MS in an ion selective mode. In each case, the ions obtained were consistent with the expected product and a representative example is provided. The possibility existed that although the alpha-ketoglutarate analogues are not substrates of the dehydrogenases and most of the aminotransferases investigated, they might be good inhibitors. Weak inhibition of aminotransferases and glutamate dehydrogenase was found with some of the alpha-ketoglutarate analogues. The newly available thermostable aminotransferases may have general utility in the synthesis of bulky L-amino acids from the corresponding alpha-keto acids.
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PMID:Analysis of conformationally restricted alpha-ketoglutarate analogues as substrates of dehydrogenases and aminotransferases. 1170 Sep 82

Metabolism of the common industrial gas tetrafluoroethylene in mammals results in the formation of S-(1,1,2,2)-tetrafluoroethyl-L-cysteine (TFEC), which can be bioactivated by a mitochondrial C-S lyase commonly referred to as beta-lyase. The resultant "reactive intermediate", difluorothioacetyl fluoride (DFTAF), is a potent thioalkylating and protein-modifying species. Previously, we have identified mitochondrial HSP70, HSP60, aspartate aminotransferase, and the E2 and E3 subunits of the alpha-ketoglutarate dehydrogenase (alphaKGDH) complex as specific proteins structurally modified during this process. Moreover, functional alterations to the alphaKGDH complex were also detected and implicated in the progression of injury. We report here the identification, by tandem mass spectrometry, and functional characterization of the final remaining major protein species modified by DFTAF, previously designated as P99(unk), as mitochondrial aconitase. Aconitase activity was maximally inhibited by 56.5% in renal homogenates after a 6 h exposure to TFEC. In comparison to alphaKGDH, aconitase inhibition (up to 79%) in a cell culture model for TFEC-mediated cytotoxicity was greater and preceded alphaKGDH inhibition, indicating that aconitase modification may constitute an early event in TFEC-mediated mitochondrial damage and cell death. These findings largely define the initial lesion of TFEC-mediated cell death and also have implications for the modeling of mitochondrial enzymatic architecture and the localization and identity of renal mitochondrial cysteine S-conjugate beta-lyase.
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PMID:Mitochondrial aconitase modification, functional inhibition, and evidence for a supramolecular complex of the TCA cycle by the renal toxicant S-(1,1,2,2-tetrafluoroethyl)-L-cysteine. 1202 83

The effect of weaning on a potential metabolic capacity of key enzymes involved in the energy production by porcine enterocytes was investigated. The activity of citrate synthase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, glutamate dehydrogenase, alanine aminotransferase and aspartate aminotransferase was determined in the small intestine epithelium of piglets during suckling-weaning transition. Investigations were performed on 5-week-old (suckling), 6-week-old (1st week after weaning) and 7-week-old (2nd week after weaning) piglets. The activity of glutamate dehydrogenase decreased (p < 0.05) during the 1st week after weaning, and remained numerically lower during the 2nd week after weaning than in suckling piglets. The activities of isocitrate dehydrogenase and alanine aminotransferase showed the same pattern as the glutamate dehydrogenase activity and decreased numerically during the 1st and 2nd weeks. The activities of citrate synthase and alpha-ketoglutarate dehydrogenase were numerically lower in post-weaned piglets (1st and 2nd weeks) than in suckling piglets. In contrast, the activity of aspartate aminotransferase was high and remained unchanged from week 5 to the 2nd week post-weaning. The activities of alanine and aspartate aminotransferase were positively correlated in suckling piglets (r = 0.98, p < 0.05) and at the 1st week after weaning (r = 0.99, p < 0.01). Also, both aminotransferases were positively correlated to the activity of alpha-ketoglutarate dehydrogenase in suckling piglets (r = 0.95, p < 0.05 and r = 0.95, p < 0.05) and to the activity of isocitrate dehydrogenase during the 1st week after weaning (r = 0.99, p < 0.001 and r = 0.99, p < 0.01). The results indicate additional capacity of the tricarboxylic acid (TCA) cycle for transformation of alpha-ketoglutarate from other sources than acetyl-CoA such as glutamine, glutamate and other amino acids. Further, the high activity of aspartate aminotransferase also suggests a high capacity of porcine small intestinal epithelium to provide the TCA cycle with oxaloacetate during the suckling-weaning transition.
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PMID:Activity of enzymes involved in energy production in the small intestine during suckling-weaning transition of pigs. 1211 42


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