Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothesis that amiodarone (AM) acts by inducing a local 'hypothyroid-like' state in thyroid hormone-responsive tissues was investigated in rat liver. Hypothyroid rats, pretreated orally for 8 consecutive days with AM (200 mg/kg) or water, were given a single i.p. injection of equimolar doses of T4, T3 or rT3 (1.00 to 1.20 mg/kg). Six hours later, the rats were killed and liver nuclear T3 receptor occupancy was determined. Simultaneously, the activity of two thyroid hormone-responsive enzymes was measured, together with the levels of their respective mRNAs by hybridization to specific cDNAs. The enzymes were phosphoenolpyruvate carboxykinase and glutamine synthetase. AM showed no effect on nuclear T3 receptor occupancy in rats injected with either vehicle, rT3, or T3, but it completely blocked the increase in receptor occupancy in rats injected with T4. With regard to postreceptor effects, T4 and T3 elicited an approximately two-fold increase in the levels of the mRNAs coding for the two enzymes, whereas rT3 had no effect. The increase of the two mRNAs was potentiated by AM, but this is probably secondary to an AM-induced state of anorexia. Remarkably, this potentiating effect of AM was not observed at the protein-level: enzyme activities were lower in rats pretreated with AM. AM-pretreatment thus results in lower enzyme activity to mRNA ratios for both enzymes, irrespective of hormonal treatment. Therefore, although no conclusions can be drawn about possible effects of AM at the transcriptional level, it is concluded that AM interferes with thyroid hormone responsive gene expression in rat liver at a post-transcriptional level. As a consequence, in the present experimental design the livers of AM-treated rats resemble the liver of hypothyroid rats with regard to specific enzyme activities, but not with regard to either nuclear T3 receptor occupancy or the levels of specific mRNAs.
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PMID:Effects of amiodarone on thyroid hormone-responsive gene expression in rat liver. 289 59

A 3-month-old girl presented with anorexia, failure to thrive and drowsiness. She was mildly icteric with hepatomegaly and peripheral oedema. Disordered liver function tests were associated with the biopsy appearances of a giant cell hepatitis and with a Fanconi syndrome. At the age of 16 weeks she collapsed with profound hypoglycaemia. Fasting also provoked hypoglycaemia with lactic acidaemia. She became increasingly irritable and hypotonic and, although initially liver and renal function improved, she deteriorated and died of hepatocellular failure and septicaemia. A post-mortem revealed massive fatty degeneration of the liver. The activity of phosphoenolpyruvate carboxykinase in her cultured skin fibroblasts was 16% of controls. Her brother died at the age of 4 weeks of sudden infant death syndrome.
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PMID:Mitochondrial phosphoenolpyruvate carboxykinase deficiency. 308 95

Hydrazine sulfate is an anticachexia agent which interrupts host energy wasting as a result of the malignant process. An inhibitor of gluconeogenesis at the phosphoenolpyruvate carboxykinase (PEP CK) reaction, this agent has been shown in randomized, placebo-controlled, double-blind trials to improve glucose tolerance, reduce glucose turnover, increase caloric intake, and increase or stabilize weight; in single-arm controlled trials, this agent has been shown to increase appetite, improve performance status, decrease pain, diminish anorexia, normalize laboratory indices, stabilize tumor growth, induce tumor regression, and promote survival, while inducing little to no important clinical side effects. In view of its demonstrated capacity to effect anticancer response, this drug is suggested for trial as a sole agent in early drug-resistant cancer, in combination with cytotoxic and related therapies, and in conjunction with total parenteral nutrition. It is postulated that effective control of the mechanisms associated associated with cancer cachexia may contribute to control of malignant disease.
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PMID:Hydrazine sulfate: a current perspective. 310 88

Three experiments were conducted to assess the effects of magnesium deficiency on the activities of hepatic glucose-6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FDPase) and phosphoenolpyruvate carboxykinase (PEPCK). Experiment 1 was designed to determine if magnesium deficiency interfered with the gluconeogenic response to fasting. Rats were fed either a control (C) or magnesium-deficient (MD) diet for 12 days. One-half of each group of rats was fasted for 24 hours prior to death. Hepatic enzyme activities, plasma and liver magnesium, and whole blood glucose were measured. Activities of G6Pase and PEPCK were higher in fasted group C rats compared to fed group C rats. Activity of FDPase was lower. The response was similar in the MD groups. Comparison of C and MD groups indicated that magnesium deficiency was accompanied by an increase in PEPCK activity. To verify this result and to investigate the role of anorexia in producing increased PEPCK activity, experiment 2 included a pair-fed group (PF). The results indicated that anorexia was not responsible for increased PEPCK activity in MD rats. The relation of circulating insulin and glucagon concentrations to effects of magnesium deficiency was explored in experiment 3. A decreased insulin:glucagon ratio was observed in MD rats. The results of these experiments suggest that magnesium deficiency alters PEPCK activity by affecting secretion of pancreatic hormones.
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PMID:Hepatic gluconeogenic enzymes, plasma insulin and glucagon response to magnesium deficiency and fasting. 627 7