Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cystic fibrosis (CF) is a chronic genetic disease mainly affecting the exocrine glands. Its main clinical symptoms are: abnormal production of mucus which blocks the airways, pancreatic insufficiency and increased sweat electrolytes. In the present investigation a series of enzymes and metabolites--mainly of carbohydrate metabolism--was investigated in biological fluids from CF homozygotes, CF heterozygotes and healthy controls under different conditions. CF homozygotes--and to a lesser degree CF heterozygotes--had increased activity of ribonuclease, and increased concentrations of electrolytes and lactate in their saliva and urine at rest. Saliva of CF patients also had augmented levels of protein. When healthy persons were submitted to anaerobic effort, the activity of ribonuclease and the concentrations of protein, electrolytes and lactate increased in their saliva, and thereby, mimicked the values found in the saliva of cystic fibrosis patients at rest. An abnormal response to a sucrose load was found in both CF-homozygotes and CF-heterozygotes. Greater increase in both glucose and lactate concentrations in the blood as well as a more rapid clearance of these metabolites was observed after the sucrose intake. A possible cause for these findings could be a disturbed carbohydrate metabolism in CF. Therefore, enzymes and metabolites connected to the metabolic pathway of glucose were investigated in CF fibroblasts and in animal models for CF. An increased activity of glycolytic enzymes in CF fibroblast were shown. Similar increases in activities of glycolytic enzymes were found in cells of submandibular glands of rats that were killed in a state of induced metabolic acidosis. These cells also showed increased protein and mucus contents, and elemental changes similar to those observed in fibroblasts of cystic fibrosis patients. Contrary to this, decreased activities of the enzymes of the glycolytic pathway were found in the submandibular gland of chronically reserpinized rats. The end-products of glycolysis, pyruvate and lactate, were also decreased, whereas the concentration of phosphoenolopyruvate and creatinphosphate were increased, possibly causing acidosis in the gland. Thus a disturbed glycolytic pathway in CF cells and a decreased intracellular pH might play an important role in the pathogenesis of this disease.
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PMID:Cystic fibrosis. Carbohydrate metabolism in CF and in animal models for CF. 347 61

Cystic fibrosis (CF) is the most common severe, autosomal recessive disease in Caucasians. The main clinical symptoms are all related to exocrine gland disturbances and include obstructive lung disease, pancreatic insufficiency and increased sweat electrolytes. In the present investigation fibroblasts from CF homozygotes were studied by X-ray microanalysis and were shown to have an increased calcium and a decreased sodium content, compared with fibroblasts from controls. The calcium increase was not specific for CF, since it was also found in fibroblasts from trisomy patients. The calcium abnormality could be corrected without any effect on the sodium level by treatment of CF cells with medium conditioned by normal cells. When normal cells were treated with medium conditioned by CF cells, the intracellular sodium level decreased without changes in the calcium level. Acid hydrolases were quantitatively increased in serum from CF patients but no qualitative differences, neither in thermal stability nor in isoelectric focusing patterns were found. Neither was any defect observed in the recognition marker of the hydrolases released from CF fibroblasts. CF homozygotes and heterozygotes had increased concentrations of lactate and electrolytes and increased activities of ribonuclease in their saliva and urine. The salivary concentration of protein was also elevated. When healthy controls were submitted to intensive maximal (anaerobic) exercise on a bicycle ergometer their salivary contents of lactate, ribonuclease, protein and electrolytes increased. Their saliva thus became more like that in CF patients. Indications of abnormal handling of a load dose of sucrose were found in both homozygotes and heterozygotes. Greater increases in the salivary concentrations of both glucose and lactate, but also a more rapid clearance of these metabolites were noted after the sucrose intake. Ingestion of sucrose also caused a normalization (decrease) of the salivary electrolyte content in homozygotes and heterozygotes. Evidence was thus produced to indicate a disturbance in the metabolism of carbohydrates and energy in cystic fibrosis, and it is speculated that such a disturbance might be of importance for the pathogenesis of this disease.
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PMID:Cystic fibrosis. In vitro and in vivo studies on the biochemical background to the pathogenesis. 658 81