EFFECTS OF CHRONIC-RENAL-FAILURE ON ENZYMES OF ENERGY-METABOLISM IN INDIVIDUAL HUMAN MUSCLE-FIBERS

In order to improve knowledge about the mechanisms underlying the alte rations of energy metabolism recently observed in the skeletal muscle of patients suffering from chronic renal failure, this study was desig ned to test (I) whether changes in the activity of key enzymes of ener gy metabolism occur in the muscle of these patients, and if so (2) whe ther the different muscle fiber types are equally altered in their met abolic machinery. For this, the maximum activities of 14 enzymes were measured in individual muscle fibers microdissected from biopsies of r ectus abdominis muscle obtained from seven normal subjects and seven p atients with end-stage rectal failure before renal replacement therapy . A large decrease in the activities of beta-hydroxyacyl-coenzyme A de hydrogenase, a key enzyme of the beta-oxidation pathway, of citrate sy nthase, which initiates the tricarboxylic acid cycle, and of fructose- 1,6-bisphosphatase, which contributes to the synthesis of glycogen fro m lactate, was observed in the three fiber types (slow-twitch oxidativ e, fast-twitch oxidative-glycolytic, and fast-twitch glycolytic), A sm aller reduction of the activities of phosphofructokinase and/or pyruva te kinase, two key enzymes of glycolysis, was also observed in slow-tw itch oxidative and/or fast-twitch oxidative-glycolytic fibers. These r esults demonstrate that the abnormalities of muscle energy metabolism observed in patients with chronic renal failure are due, at least in p art, to intrinsic changes in the key enzymes of major energy-providing pathways; they also offer a satisfactory explanation for the defect o f oxidative metabolism recently demonstrated in the muscle of these pa tients.