Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reports a study of changes in red blood cell enzymes and some serum parameters during and after treatment of protein-calorie malnutrition. The red cell GSH levels were low during the crisis, together with the levels of GSSG:NADPH reductase, GSH:H2O2 peroxidase, aspartate aminotransferase and alanine aminotransferase. After treatment the levels of all these enzymes increased significantly to normal values. Of the serum parameters investigated, significant reduction in the activity of the enzymes cholinesterase, catecholamine oxidase, total proteins, albumin, urea and electrolytes were obvious, and returned to normal values after treatment. Ceruloplasmin activity remained low even after three weeks' treatment and could not be related to copper levels. The results are discussed in relation to anemia and liver damage that may accompany the syndrome.
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PMID:Protein-calorie malnutrition: a study of red blood cell and serum enzymes during and after crisis. 82 Apr 94

Wistar rats received an hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, a halogenated pyrrole designated PD 123244-15, orally by gavage for 14 days at 10, 50, 150, 300, and 600 mg/kg. Doses of 150-600 mg/kg caused death and marked systemic toxicity involving stomach, esophagus, liver, gonads, lymphoid tissues, and skeletal muscle. Histopathologic findings included hyperkeratosis in esophagus and forestomach, increased hepatic mitotic activity, ovarian follicular necrosis, testicular atrophy and arrested spermatogenesis, and skeletal muscle necrosis and regeneration. Elevated serum aspartate aminotransferase correlated with muscle necrosis and hepatocellular damage. Marked systemic effects associated with high plasma concentrations were consistent with toxicity defined for other HMG-CoA reductase inhibitors, with the exception of pathologic alterations in the esophagus and ovaries. Direct mucosal irritation may have contributed to forestomach and esophageal lesions induced by this halogenated pyrrole.
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PMID:Subacute toxicity of a halogenated pyrrole hydroxymethylglutaryl-coenzyme A reductase inhibitor in Wistar rats. 130 25

Since fumarate and nitrate are not usually available in the oral ecosystem, it was investigated whether aspartate and asparagine could be used as alternative electron acceptors by Wolinella recta, which is strictly dependent on a respiratory metabolism with formate or H2 as electron donors. Both aspartate and asparagine were indeed shown to support growth of W. recta with formate as electron donor. Fermentative growth with aspartate alone was not possible. Succinate was the major end-product and was formed in equimolar quantities with respect to the amount of formate consumed. The consumption of aspartate and asparagine, on a molar basis, was 10-30% higher than that of formate. Cell-free extracts were prepared from cells grown with formate + fumarate, formate + aspartate, formate + asparagine, and formate + fumarate + aspartate. All these extracts contained high activities of asparaginase, aspartate ammonia-lyase and fumarate-reductase, but no significant activity of aspartate aminotransferase was detected, indicating that fumarate was synthesized directly from aspartate and subsequently reduced to succinate. Based on these results it seems likely that aspartate and asparagine can serve as natural electron acceptors for W. recta in periodontal lesions in which proteolytic bacteria abound.
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PMID:Aspartate and asparagine as electron acceptors for Wolinella recta. 194 91

A method for the purification of chicken liver soluble aspartate aminotransferase, lactate dehydrogenase free, is proposed. The preparation, which contained a mixture of the five molecular forms of the enzyme, showed a 120-fold increase in specific activity, with respect to the initial homogenates. Differences in Km(2-oxoglutarate) and saturating concentrations among solutions of purified enzyme and soluble fraction were due to the 2-oxoglutarate reductase activity of lactate dehydrogenase.
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PMID:Modification of the kinetic parameters of chicken liver cytoplasmic aspartate aminotransferase by lactate dehydrogenase. 405 24

1. In order to assess the effects of oestrogens on the metabolism of tryptophan and vitamin B6, ovariectomized rats have been maintained on diets providing known amounts of tryptophan, nicotinamide and vitamin B6. They received oestrone sulphate, 210 micrograms/kg body-wt per d, either incorporated in the diet for 8 weeks, or by daily intraperitoneal injection for periods of 1-3 d. 2. Oestrone sulphate administration caused a slight reduction in the concentration of pyridoxal phosphate in plasma. It had no effect on the concentration of pyridoxal phosphate in liver or kidney, the urinary excretion of 4-pyridoxic acid, the activation of erythrocyte aspartate aminotransferase (L-aspartate:2-oxo-glutarate aminotransferase, EC 2. 6. 1. 1) by incubation with added pyridoxal phosphate, or the activity of pyridoxal oxidase (aldehyde:oxygen oxido-reductase, EC 1.2.3.1) in the liver. 3. Oestrone sulphate administration caused an increase in the urinary excretion of kynurenine and a reduction in the activity of liver kynureninase (L-kynurenine hydrolase, EC 3.7.1.3). It had no effect on the urinary excretion of N1-methyl nicotinamide or the concentrations of nicotinamide nucleotides in blood, liver or kidney. 4. There was a considerable excess of the apoenzyme of kynureninase in the liver. Incubation of liver homogenates with added pyridoxal phosphate led to a 4- to 5-fold increase in activity. 5. We conclude that there is no evidence of any significant effect of oestrogens on vitamin B6. It is suggested that abnormalities of tryptophan metabolism in women receiving oestrogens, which have been widely attributed to drug-induced vitamin B6 depletion, can be accounted for by inhibition of kynureninase by oestrogen metabolites.
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PMID:Effects of oestrogen administration on vitamin B6 and tryptophan metabolism in the rat. 628 3

Unlike erythrocytes from elderly humans, red blood cells from old mice are not more sensitive than are cells from young animals to lysis in hypotonic solutions, probably because the mean corpuscular volume decreases rather than increases with age in this species. However, when subjected to an oxidant stress (sodium ascorbate) red blood cells from old animals accumulate more methemoglobin and fewer remain intact than is the case with red blood cells from young mice. The data suggest that this increased vulnerability to oxidative damage is manifest relatively early in the lifespan of red blood cells from old animals and is not solely a property of the older cells. The pathogenesis of the decreased resistance to peroxidation is not known, but it does not appear to be the result of changes in reduced glutathione, NADH: methemoglobin reductase, superoxide dismutase, glutathione reductase, glutamic-oxaloacetic transaminase, or glucose 6-phosphodehydrogenase.
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PMID:Age-related increase in erythrocyte oxidant sensitivity. 717 1

Pravastatin, lovastatin, and simvastatin, drugs which lower cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, have been linked to skeletal myopathies in humans and rats. The myotoxicity of these three drugs was compared, after 48 hr exposure, in cultures of primary neonatal rat skeletal myotubes. Measurements included HMG CoA reductase activity ([14C]acetate incorporation into cholesterol), indicators of membrane damage (CPK, LDH, and AST), cell viability (mitochondrial dehydrogenase metabolism of MTT), protein synthesis ([3H]leucine incorporation), and energy status (ATP). All three drugs inhibited cholesterol synthesis to the same extent in rat hepatocytes (IC50s approximately 0.07 microM). Lovastatin- and simvastatin-induced inhibition of cholesterol synthesis in myotubes was unchanged compared to that of hepatocytes, but pravastatin was 85-fold less potent (IC50 = 5.9 microM). Protein synthesis and ATP levels were the most sensitive indicators of toxicity. Pravastatin (IC50 = 759 microM) was > 100-fold less inhibitory of protein synthesis than lovastatin (IC50 = 5.4 microM) or simvastatin (IC50 = 1.9 microM). Addition of mevalonic acid (the immediate product of the HMG CoA reductase reaction), as 100 microM mevalonic acid lactone, reversed the toxicity of all three drugs. Removal of serum for 24-72 hr did not alter the toxicity of any of the drugs compared to cultures containing 10% serum, suggesting that differences in protein binding did not account for the differences in toxicity of the drugs. These results indicate that pravastatin is less myotoxic than lovastatin or simvastatin in this in vitro system using neonatal rat skeletal muscle cells, and this differential toxicity is correlated with the selective decrease in inhibition of HMG CoA reductase by pravastatin in nonhepatic tissues.
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PMID:In vitro myotoxicity of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, pravastatin, lovastatin, and simvastatin, using neonatal rat skeletal myocytes. 787 72

The coexistence of hypercholesterolemia and hypertension often requires concomitant drug treatments. Thus, it is interesting to evaluate the efficacy, safety, and tolerability of the new lipid-lowering agent fluvastatin, a 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA)-reductase inhibitor, in patients receiving concomitant antihypertensive/cardiovascular drug treatments. A retrospective analysis was based on data from controlled clinical trials in which 1815 patients were treated with fluvastatin and 783 patients received placebo. The daily dose of fluvastatin was > or = 20 mg. At least one of the following drug treatments was taken by 445 of the fluvastatin-treated patients (24.5%) and 181 of those receiving placebo (23.1%): beta-adrenergic-receptor blockers (fluvastatin: n = 182; placebo: n = 84); diuretics (fluvastatin: n = 168; placebo: n = 72); calcium antagonists (fluvastatin: n = 161; placebo: n = 69); and angiotensin-converting enzyme (ACE) inhibitors (fluvastatin: n = 101; placebo: n = 30). The majority of patients received monotherapy with one of the above-mentioned antihypertensive agents (fluvastatin: 69%; placebo: 65%). The efficacy of fluvastatin in modifying low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol and triglyceride levels was not consistently different in patients taking a given antihypertensive compared with the overall group and the patients not taking the antihypertensive agent. In patients taking fluvastatin and antihypertensives, confirmed (measured at two consecutive occasions) increases more than three times the upper limit of normal in aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) occurred in only two patients. One case involved the concomitant use of a beta-blocker (ASAT and ALAT) and the other a diuretic (ALAT).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Safety and tolerability of fluvastatin with concomitant use of antihypertensive agents. An analysis of a clinical trial database. 790 74

1. GR95030X, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was administered daily to marmosets by gavage. In a Maximum Repeatable Dose (MRD) study, doses of up to 30 mg kg-1 day-1 were administered for 49 days. In a chronic study, animals received dosages equivalent to 0, 1, 2.5, 7.5 and 20 mg kg-1 day-1 for 204 or 205 days. Some animals were maintained without treatment for a recovery period of 29 or 30 days. 2. Clinical signs included poor coat condition, weakness with impaired coordination, lethargy and other behavioural changes. There was also alimentary disturbance, and some deaths occurred at doses of 20 mg kg-1 day-1 and above. 3. Adverse effects upon body weight were seen although some recovery was apparent after the cessation of treatment. 4. Serum cholesterol concentrations were reduced. Very large increases in serum ALT, AST and CK activities were recorded with CK-MM isoenzymes accounting for 80% or more of the total CK enzyme activity. 5. Treatment was associated with muscle fibre atrophy and a sarcolemmal response with little evidence of regeneration. Histological examination revealed vascular changes, glial proliferation and cell death in the brain, with no consistent distribution. Alveolar capillary congestion and alveolar proteinosis indicated that there may have been a reduction in cardiac function. 6. HMG-CoA reductase inhibitors have evident potential to cause myopathy in marmosets. This is believed to be the first report of such an effect.
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PMID:Toxicity of a novel HMG-CoA reductase inhibitor in the common marmoset (Callithrix jacchus). 804 18

The concurrence of hypertension and hypercholesterolemia leads to the clinical need to lower lipids in hypertensive patients. Thus, it is interesting to evaluate the efficacy and safety of fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)-reductase inhibitor, in such a patient population. A retrospective analysis of the clinical efficacy and safety of fluvastatin was based on the data from 1815 patients who received fluvastatin at daily doses of > or = 20 mg compared with 783 patients taking placebo. The results showed that 332 (18.3%) of the fluvastatin-treated and 124 (15.8%) of the placebo-treated patients were identified as having hypertension. The percentage change from baseline of low-density lipoprotein cholesterol (LDL-C) in hypertensive patients taking fluvastatin at doses of 20 and 40 mg/day was -20% and -26%, respectively (placebo: 1.4%), and did not differ from the response in non-hypertensive patients. Increases in high-density lipoprotein cholesterol (HDL-C) as well as decreases in triglycerides with fluvastatin were not consistently different between hypertensive and non-hypertensive patients. Irrespective of the presence or absence of hypertension, confirmed (measured on two consecutive occasions) increases > three times the upper limit of normal in aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were observed in three (0.2%) and 12 (0.7%) patients, respectively. With placebo, ALAT was increased in two patients (0.2%). The incidence of notable increases more than 10 times the upper limit of normal in creatine kinase was similar with fluvastatin compared with placebo (0.3% in both).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy and safety of fluvastatin in hypertensive patients. An analysis of a clinical trial database. 829 42


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