Cystic fibrosis. Carbohydrate metabolism in CF and in animal models for CF.

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.