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)

Both the mouse cytosolic malate dehydrogenase gene and its mitochondrial counterpart contain eight introns, of which two are present at identical positions between the isozyme genes. The probability that the two intron positions coincide by chance between the two genes has been shown to be significantly small (= 1.3 x 10(-3), suggesting that the conservation of the intron positions has a biological significance. On the basis of a rooted phylogenetic tree inferred from a comparison of these isozymes and lactate dehydrogenases, we have shown that the origins of the conserved introns are very old, possibly going back to a date before the divergence of eubacteria, archaebacteria, and eukaryotes. In the aspartate aminotransferase isozyme genes, five of the introns are at identical places. The origins of the five conserved introns, however, are not obvious at present. It remains possible that some or all of the conserved introns have evolved after the divergence of eubacteria and eukaryotes.
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PMID:Compartmentalized isozyme genes and the origin of introns. 212 Apr 56

The malate-aspartate shuttle, consisting of mitochondrial and cytosolic aspartate aminotransferase and mitochondrial and cytosolic malate dehydrogenase, is a major pathway for the transport of reducing equivalents from cytosol to mitochondria in mammals. To elucidate molecular mechanisms regulating metabolic coordination between the mitochondria and the cytosol, we analyzed the 5'-flanking regulatory regions of the complete set of mouse isoenzyme genes playing a pivotal role in the shuttle. Deletion analysis and an in vivo transfection assay, using NIH3T3 cells, revealed that all the promoter regions are located within the 300-base pair regions upstream from the initiation codon. Subsequently, DNase I footprinting analyses using NIH3T3 cell nuclear extracts led to identification of several protein binding sites within these promoter regions. A synthetic oligomer containing the consensus binding site sequence for CTF/NFI, a transcription factor for RNA polymerase II, competed for the binding of proteins to the promoter regions of cytosolic aspartate aminotransferase and mitochondrial and cytosolic malate dehydrogenase genes, but not for that of the mitochondrial aspartate amino-transferase gene. On the other hand, a synthetic oligomer containing the consensus binding site sequence for Sp1, which activates transcription from promoters containing properly positioned GC boxes, competed for protein(s) binding to the promoter region of the mitochondrial aspartate aminotransferase gene.
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PMID:Regulatory regions of the mitochondrial and cytosolic isoenzyme genes participating in the malate-aspartate shuttle. 229 30

We have previously shown that the rapid clearance of intravenously injected lactate dehydrogenase M4 from plasma is mainly due to endocytosis by macrophages in liver, spleen, and bone marrow. We have now studied endocytosis of lactate dehydrogenase M4 in detail, using freshly isolated rat liver macrophages (Kupffer cells) in vitro. 125I-lactate dehydrogenase M4 rapidly accumulated in the cells and was subsequently degraded to trichloroacetic acid-soluble material. Degradation was inhibited by leupeptin, an inhibitor of lysosomal proteases. Breakdown of the protein was also greatly diminished by treatment of the cells with chloroquine, a weak base which inhibits proteolysis by raising the pH in endosomes and lysosomes. High concentrations of chloroquine inhibited uptake. Lactate dehydrogenase M4 was not endocytosed by liver endothelial cells, although, under the same conditions, these cells were shown to accumulate horse radish peroxidase via a mannose-specific receptor. Uptake of lactate dehydrogenase M4 by Kupffer cells was strongly reduced after pretreatment of the cells with low concentrations of proteases. Endocytosis of lactate dehydrogenase M4 exhibited saturation kinetics (Km = 0.8 microM) and was competitively inhibited by mitochondrial and cytosolic malate dehydrogenase, alcohol dehydrogenase, adenylate kinase, and creatine kinase MM, enzymes which are rapidly cleared in vivo. Enzymes with long half-lives in plasma, namely lactate dehydrogenase H4, alanine aminotransferase, and cytosolic aspartate aminotransferase did not compete at concentrations up to 10 microM. Our results indicate that Kupffer cells contain a receptor that is involved in the clearance of lactate dehydrogenase M4 and a number of other tissue-derived enzymes from plasma. Uptake of lactate dehydrogenase M4 does not occur via a receptor that recognizes carbohydrate residues, for the enzyme is not a glycoprotein.
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PMID:Receptor-mediated endocytosis of lactate dehydrogenase M4 by liver macrophages: a mechanism for elimination of enzymes from plasma. Evidence for competition by creatine kinase MM, adenylate kinase, malate, and alcohol dehydrogenase. 282 Sep 61

Polarographic assays of oxidative phosphorylation in muscle mitochondria indicated abnormal pyruvate-malate metabolism in Friedreich ataxia (FA). Pursuing this clue, more specific assays were performed. Mitochondrial malic enzyme (MEm; malate: NADP+ oxidoreductase) specific activity was 10% of controls in fibroblasts from eight FA patients (p less than 0.0001). Cytosolic malic enzyme was modestly increased in FA fibroblasts. Mitochondrial and cytosolic malate dehydrogenase and aspartate aminotransferase, and malate transport on the dicarboxylate and alpha-ketoglutarate carriers were normal in fibroblasts or leukocytes. MEm activity is normally highest in the nervous system and heart is important in regulating carbohydrate metabolism. MEm deficiency could cause FA; further studies are required to substantiate this hypothesis.
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PMID:Friedreich ataxia: III. Mitochondrial malic enzyme deficiency. 719 31

The interactions between pig heart citrate synthase and mitochondrial malate dehydrogenase or cytosolic malate dehydrogenase were studied using the frontal analysis method of gel filtration and by precipitation in polyethylene glycol. This method showed that an interaction between citrate synthase and mitochondrial malate dehydrogenase occurred but no interaction between citrate synthase and cytosolic malate dehydrogenase. Channeling of oxaloacetate in the malate dehydrogenase and citrate synthase-coupled systems was tested using polyethylene glycol precipitates of citrate synthase and mitochondrial malate dehydrogenase, and citrate synthase and cytosolic malate dehydrogenase. The effectiveness of large amounts of aspartate aminotransferase and oxaloacetate decarboxylase, as competing enzymes for the intermediate oxaloacetate, was examined. Aspartate aminotransferase and oxaloacetate decarboxylase were less effective competitors for oxaloacetate when precipitated citrate synthase and mitochondrial malate dehydrogenase in polyethylene glycol was used at low ionic strength compared with free enzymes in the absence of polyethylene glycol or with a co-precipitate of citrate synthase and cytosolic malate dehydrogenase. Substrate channeling of oxaloacetate with citrate synthase-mitochondrial malate dehydrogenase precipitate was inefficient at high ionic strength. These effects could be explained through electrostatic interactions of mitochondrial but not cytosolic malate dehydrogenase with citrate synthase.
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PMID:Interaction between citrate synthase and malate dehydrogenase. Substrate channeling of oxaloacetate. 979 62

The normal endogenous level of malate-aspartate shuttle enzymes and its regulation by hydrocortisone and triiodothyronine were studied in the liver and kidney of 0-, 30- and 60-day old male Rhode Island Red (RIR) chicken. The endogenous activity of cytosolic malate dehydrogenase (c-MDH) was significantly higher in the liver of day 30 as compared to day 0 and 60. In contrast, mitochondrial malate dehydrogenase (m-MDH) activity decreased at day 60 in the liver. However, both c- and m-MDH had significantly lower activities at day 0, which increased sharply at day 30 and 60 in the kidney. On the other hand, activity of both cytosolic and mitochondrial aspartate aminotransferase (c- and m-AsAT) showed peak value at day 30 in both liver and kidney. Hydrocortisone administration induced c-MDH in the liver at all the ages studied, but did not influence the activity of the isoenzymes in the kidney whereas, it induced m-MDH in the liver at day 0 and in kidney at day 30. Administration of hydrocortisone, however, did not influence AsAT isoenzymes (c- and m-AsAT) in either of the tissues at any of the postnatal ages. Triiodothyronine induced c-MDH in the liver at all the ages whereas kidney isoenzyme was induced only at day 60. In contrast, m-MDH was induced by triiodothyronine in both liver and kidney at day 30 and 60. Administration of triiodothyronine did not influence c-AsAT of liver and kidney at either of the ages, whereas it induced m-AsAT of only liver at day 0 and 60. These findings indicated a tissue- and age-specific expression of the malate-aspartate shuttle enzymes in chicken and difference in the regulation exerted by hydrocortisone and triiodothyronine during postnatal development of chicken.
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PMID:Hydrocortisone and triiodothyronine regulation of malate-aspartate shuttle enzymes during postnatal development of chicken. 1169 80