Energy production, intracellular amino acid pools, and protein synthesis in chronic renal disease

Abstract

Intracellular glycolytic regulating enzyme activities, pyruvate kinase (PK) and phosphofructokinase (PFK), adenylate kinase (AK), energy charge (Ech), free amino acids (ICAA), and protein synthesis (PS) were measured in polymorphonuclear leukocytes--used as a cell model--in 62 adults and 12 children with chronic renal failure, and 66 normal adults and 21 children as comparison controls. In normal subjects, children had significantly lower enzyme activities and cell amino acid levels but similar Ech and higher PS than adults. ICAA concentrations were significantly higher than plasma amino acid concentrations (PAA) in both groups, and the PAA were not correlated with, nor indicative of, the ICAA concentrations. The variance (R2) in PS could be largely accounted for by a combination ("set") of six ICAA, as determined by multivariate analysis. The sets differed in children vs adults, suggesting that different proteins were being synthesized. In the uremic patients, reduced PF, PFK, Ech, most ICAAs and PS were indicative of cellular malnutrition. For the uremic adults, the abnormalities in cell metabolism were modified by therapy--nondialyzed uremics being worst, CAPD patients best and approximately normal, and hemodialyzed intermediate. The uremic CAPD children had reduced, PK, PFK, AK, most ICAA, and PS. Ech was increased. Cellular malnutrition in children with chronic renal failure may contribute to their poor growth.