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)

Cytoplasmic proteins are degraded with different half-lives in vivo. Large parts of proteins are believed to be degraded primarily in autophagic vacuoles-lysosomal system. However, the mechanism by which cell proteins are delivered to lysosomes and whether such a process might be selective for certain cell proteins are still unresolved. We examined the mechanism of autophagy with isolated autophagic vacuoles. Administration of leupeptin, a inhibitor of lysosomal thiol proteinases, induced the accumulation of numerous autophagic vacuoles in the liver. Highly purified preparation of autophagic vacuoles was isolated by Percoll density gradient equilibrium fractionation of crude lysosomal fractions. When cytosolic enzyme activities in autophagic vacuoles were measured, tyrosine aminotransferase and tryptophan oxygenase with short half-lives, and lactic dehydrogenase and aspartate aminotransferase with long half-lives were detected at similar ratios of enzymes in autophagic vacuoles/cytosol. During the time that cathepsin B plus L activities in autophagic vacuoles are inhibited by the injection of leupeptin, cytosolic enzymes are being accumulated in autophagic vacuoles suggesting that leupeptin blocks intralysosomal proteolysis, and that cytosolic enzymes are sequestered continuously into autophagosomes. Administration of glucocorticoid, which induces the synthesis of tyrosine aminotransferase, tryptophan oxygenase and cytosolic aspartate aminotransferase, selectively increased the sequestration of these enzymes to proportional degrees. Dietary manipulation and administration of insulin, which inhibit the formation of autophagic vacuoles, suppressed completely the accumulation of autophagic vacuoles in liver by administration of leupeptin. Results indicate that there is no selective uptake of cytosolic enzymes into autophagosome. When distribution of lysosomal cathepsin B and L in liver, which are inhibited strongly by leupeptin, was examined immunohistochemically, cathepsin L is found only in hepatocytes, but cathepsin B is localized in sinusoidal cells rather than in hepatocytes, suggesting that cathepsin L plays a most important role in intralysosomal proteolysis in hepatocytes.
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PMID:Lysosomal sequestration of cytosolic enzymes and lysosomal thiol cathepsins. 390 2

Regionally selective and time-dependent variations were observed in the activity of brain aspartate aminotransferase at early phases of diabetes. Malate dehydrogenase activity showed an opposite pattern of changes in soluble and particulate fractions of cerebral hemispheres and brain stem, with cerebellum showing consistent increase in the activity. The activity of both the enzymes increased significantly in liver, in contrast to heart where malate dehydrogenase activity decreased in particulate fraction. Insulin treatment to diabetic animals restored the enzymes to near control levels at early stages of diabetes, except in liver. The results indicate that malate-aspartate shuttle is probably stimulated under diabetic conditions to enable glycolysis to continue and ATP levels to be restored partially, particularly in cerebellum and liver.
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PMID:Malate-aspartate shuttle enzymes in rat brain regions, liver and heart during alloxan diabetes and insulin replacement. 391 Apr 26

1. A method is described for extracting separately mitochondrial and extramitochondrial enzymes from fat-cells prepared by collagenase digestion from rat epididymal fat-pads. The following distribution of enzymes has been observed (with the total activities of the enzymes as units/mg of fat-cell DNA at 25 degrees C given in parenthesis). Exclusively mitochondrial enzymes: glutamate dehydrogenase (1.8), NAD-isocitrate dehydrogenase (0.5), citrate synthase (5.2), pyruvate carboxylase (3.0); exclusively extramitochondrial enzymes: glucose 6-phosphate dehydrogenase (5.8), 6-phosphogluconate dehydrogenase (5.2), NADP-malate dehydrogenase (11.0), ATP-citrate lyase (5.1); enzymes present in both mitochondrial and extramitochondrial compartments: NADP-isocitrate dehydrogenase (3.7), NAD-malate dehydrogenase (330), aconitate hydratase (1.1), carnitine acetyltransferase (0.4), acetyl-CoA synthetase (1.0), aspartate aminotransferase (1.7), alanine aminotransferase (6.1). The mean DNA content of eight preparations of fat-cells was 109mug/g dry weight of cells. 2. Mitochondria showing respiratory control ratios of 3-6 with pyruvate, about 3 with succinate and P/O ratios of approaching 3 and 2 respectively have been isolated from fat-cells. From studies of rates of oxygen uptake and of swelling in iso-osmotic solutions of ammonium salts, it is concluded that fat-cell mitochondria are permeable to the monocarboxylic acids, pyruvate and acetate; that in the presence of phosphate they are permeable to malate and succinate and to a lesser extent oxaloacetate but not fumarate; and that in the presence of both malate and phosphate they are permeable to citrate, isocitrate and 2-oxoglutarate. In addition, isolated fat-cell mitochondria have been found to oxidize acetyl l-carnitine and, slowly, l-glycerol 3-phosphate. 3. It is concluded that the major means of transport of acetyl units into the cytoplasm for fatty acid synthesis is as citrate. Extensive transport as glutamate, 2-oxoglutarate and isocitrate, as acetate and as acetyl l-carnitine appears to be ruled out by the low activities of mitochondrial aconitate hydratase, mitochondrial acetyl-CoA hydrolyase and carnitine acetyltransferase respectively. Pathways whereby oxaloacetate generated in the cytoplasm during fatty acid synthesis by ATP-citrate lyase may be returned to mitochondria for further citrate synthesis are discussed. 4. It is also concluded that fat-cells contain pathways that will allow the excess of reducing power formed in the cytoplasm when adipose tissue is incubated in glucose and insulin to be transferred to mitochondria as l-glycerol 3-phosphate or malate. When adipose tissue is incubated in pyruvate alone, reducing power for fatty acid, l-glycerol 3-phosphate and lactate formation may be transferred to the cytoplasm as citrate and malate.
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PMID:The intracellular localization of enzymes in white-adipose-tissue fat-cells and permeability properties of fat-cell mitochondria. Transfer of acetyl units and reducing power between mitochondria and cytoplasm. 439 82

16 patients with carcinoma of the endometrium were treated with 50-mg medroxyprogesterone im twice daily for 1 year and studied to determine what effect this high dose of progesterone had on carbohydrate metabolism and liver function. Oral glucose tolerance values (fasting and 2 hour) were significantly elevated (p less than .001) at 12 and 18 months. Conjugated bilirubin was significantly elevated (p less than .01) at 18 months, aspartate aminotransferase was significantly elevated (p less than .001) at 12 and 18 months. Insulin values were raised transiently at 3 months. It is conluded that the changes in carbohydrate and liver function were small, appeared slowly, and included only a few pathologically elevated values; consequently the use of high-dose progestogen treatment for a 1-year period is considered safe.
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PMID:Effects of high-dose medroxyprogesterone treatment given for endometrial carcinoma on carbohydrate metabolism and liver function. 485 52

Serum chemical values were determined in cold-stressed Holstein bull calves ranging from 1 to 7 days of age. The animals were anesthetized and cold-stressed until their core body temperature (colonic) was lowered 10 C. Animals were then rewarmed in warm water, with heat pads or heat lamps, or were allowed to recover naturally (unassisted) at room temperature. Blood samples were collected at selected intervals during cooling and recovery. Increases (P less than 0.05) were observed in the concentrations of glucose, calcium, phosphorus, iron, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, total protein, albumin, total globulin, serum urea nitrogen, uric acid, total bilirubin, indirect bilirubin, and cholesterol in the cold-stressed calves during cooling. Concentrations of chloride and insulin decreased (P less than 0.05) during the same period. Changes observed in many of the serum chemical values during rewarming were generally the reverse of the respective changes that occurred during cooling, although insulin values became exceedingly high in some cases midway or near the end of recovery. Serum enzyme values also remained high during most of recovery. Data did not indicate a clear advantage of one method of rewarming over the other methods used in terms of return of the serum chemical values to normal.
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PMID:Serum chemical values in hypothermic and rewarmed young calves. 634 64

Total proteins (albumin, globulins and their fractions); carbohydrate (intravenous glucose tolerance); lipid (serum cholesterol, triglycerides, and phospholipids); and liver functioning (alkaline phosphatase, lactic dehydrogenase, and aspartate aminotransferase activities in serum, bromsulfathalein retention, and serum bilirubin); were assayed in 12 Thai women who were not lactating. The tests were performed before, and 3 weeks, 3,6,9, and 12 months after the advent of treatment with medroxyprogesterone acetate (DMPA), which was injected intramuscularly in 150-mg doses every 90 days. Triglyceride concentration was unchanged overall; however, mean fasting triglyceride concentration on Day 20 decreased significantly when compared with Day -33 pretreatment control (P .025). A significant increase ( P .01) in mean fasting cholesterol was demonstrated on Day 20; this, however, was thought to be caused by the high dietary lipid intake during hospitalization rather than an effect of the DMPA. In general, serum protein and lipid levels, and liver function and glucose tolerance, remained unchanged over 1 year. There was, however, a significant and persistent increase in insulin level in all subjects after initiation of hormone treatment during the first 30 minutes of intravenous glucose load. The study concludes that DMPA does not interfere with glucose tolerance, lipid and protein metabolism, or liver function during its administration.
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PMID:Effects of medroxyprogesterone acetate on serum lipids, protein, glucose tolerance and liver function in Thai women. 644 43

The animals examined were 30 sows after eleven or more farrowings (pluriparous sows) and 26 primiparous sows. The pluriparous animals were 75.1 months old on the average and had farrowed an average of 13.23 litters. The mean age of the primiparous sows was 12.8 months. The blood sera of pluriparous sows had higher concentrations of total protein and urea and lower levels of 11-hydroxycorticosteroids (11-OHCS) and lower aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities than those of primiparous sows. The pluriparous sows showed mild hypoglycaemia and hypocholesterolaemia. When insulin was injected i.m. in the dose of 1 I.U. per kg body mass, a decrease in blood serum glucose, total protein and potassium levels was recorded 60 min later in both pluriparous and primiparous sows; a significant rise in 11-OHCS concentration occurred only in the primiparous sows. It was concluded that the response of the hypothalamo-pituitary-adrenal axis in pluriparous sows to an insulin load is reduced. Studies of pluriparous sows contribute to a better understanding of the ontogenetic development of pigs throughout their postnatal development.
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PMID:Biochemical changes in sows after eleven or more farrowings. 670 30

Acute hepatic ischaemia was induced in pigs by means of a portacaval shunt with hepatic artery ligation after 24 hours. Despite significant elevation in blood ammonia, fatty acids, aspartate aminotransferase, cerebrospinal fluid glutamine and ammonia, and brain tissue glutamine, ammonia and tryptophan, the experimental animals remained awake and alert and indistinguishable from sham-operated controls. The molar ratio of branched-chain to aromatic amino acids fell sharply in the arterial blood, but showed a terminal attempt at compensation in muscle venous samples. Portal and muscle venous insulin levels were elevated, and glucagon values rose in all circulation segments in the experimental group. The failure to induce coma in these pigs, despite the presence of many of the classical biochemical features, suggests that the syndrome of encephalopathy comprises several stages, and that the pig may be an important model in which to define these.
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PMID:Acute hepatic ischaemia in the pig- the changes in plasma hormones, amino acids and brain biochemistry. 725 Aug 93

The zonation of the expression and regulation of the cytosolic aspartate aminotransferase (cAspAT) mRNAs in the liver acinus was investigated in diabetic and/or adrenalectomized rats. Dexamethasone increased cAspAT activity two- to threefold alone and up to sixfold in combination with streptozotocin-induced diabetes. Northern blot analysis showed that the cAspAT mRNAs were increased by those treatments; the effect of streptozotocin was reversed by the administration of insulin. In situ hybridization experiments showed that basal cAspAT mRNAs were uniformly distributed within the liver acinus. However, cAspAT mRNAs were induced by glucocorticoids specifically in the periportal zone and by streptozotocin in a larger area including the periportal and intermediary zone. The alpha 2u-globulin mRNAs which are specifically expressed in the perivenous hepatocytes are also induced by glucocorticoids in this zone, suggesting that the specific regulation of the cAspAT gene by glucocorticoids in the periportal zone is not due to the absence of functional glucocorticoid receptors in the other zones. We conclude that the regulation of the cAspAT housekeeping gene is zone specific in the liver. Furthermore, this zonation depends on the gene and on the type of hormonal or pharmacological treatment.
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PMID:Acinar zonation of the hormonal regulation of cytosolic aspartate aminotransferase in the liver. 751 55

The hypothesis was tested that goats allowed ad libitum access to feed during the dry period develop higher post partum hepatic triacylglycerol concentrations than do goats given a restricted amount of feed during the dry period. Goats in their second or more pregnancies were either given a restricted amount of hay, maize silage and concentrate (n = 5) or had free access to this feed mixture while the composition was kept constant (n = 11). After parturition both groups were allowed ad libitum access to feed. Post partum liver triacylglycerol concentrations, as measured in liver biopsies, were significantly raised in goats allowed ad libitum access to feed during the dry period. The increase in liver triacylglycerols was associated with slightly higher plasma concentrations of non-esterified fatty acids but lower serum 3-hydroxybutyrate concentrations. The feeding regimen during the dry period did not significantly influence post partum liver glycogen concentrations and serum levels of glucose, cholesterol, and insulin. The increase in post partum liver triacylglycerol concentrations in the goats allowed ad libitum access to feed instead of a restricted ration during the dry period, was associated with a significant rise in serum alkaline phosphatase activities, whereas other liver function and cell damage indicators in serum, i.e. aspartate aminotransferase, lactate dehydrogenase, gamma glutamyl transpeptidase, and bilirubin, were unchanged. Feed intake after parturition tended to be higher in the goats allowed ad libitum access to feed during the dry period but milk production was significantly raised.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liver triacylglycerol concentrations around parturition in goats with either pre-partum restricted or free access to feed. 757 Dec 80


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