Abstract
To improve protein synthesis (PS) and Energy charge (Ech) should require correction of imbalanced intracellular amino acid levels. In 40 adult chronic uremics stabilized by hemodialysis, multiple regression analysis identified combinations of cell amino acid levels predicting intracellular PS (3 H-Leucine incorp) (PS=10.8 + 0.02 ASP -0.127 VAL + 0.54 ILE + 0.032 ORN -0.12 LYS -0.10 TRP (R2= 0.40, p=0.019)) and Energy charge (Ech=ATP + 1/2 ADP/ATP + ADP + AMP) (Ech (x 103) = 766 -0.75 ASP + 0.18 GLU + 0.59 GLY + 0.53 ORN -0.33 ARG (R2=0.33, p=0.036)). PS and Ech were reduced compared to 32 normals. The leukocyte (∼90% Pm neutrophils) was used as the cell model. 18 adult chronic uremics, stabilized on 3x/wk hemodialysis, were infused with 500ml 10% amino acid solution after each dialysis, dialyzer detached, for 3 months, receiving in toto ≅ 1.5-1.9kg synthetic amino acids. Baseline studies showed decreased (p<.05) PS, Ech and in vitro glycolytic flux (glucose → lactate). The amino acid infusions led to decreased blood pressure and plasma cholesterol level, but did not significantly improve cell bioactivities. The intracellular amino acid imbalance worsened: valine, isoleucine, leucine, methionine, lysine and ornithine were reduced; arginine + glycine were increased. Only tyrosine and phenylalanine levels normalized. We ascribe failure to correct cell bioactivities to failure to correct the cell amino acid imbalance. The leukocyte is a useful cell model to formulate and evaluate therapies to correct abnormal cell metabolism in uremics.
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Metcoff, J., Dutta, S., Burns, G. et al. PROTEIN SYNTHESIS, ENERGY LEVEL AND CELL AMINO 1617 ACID IMBALANCE IN CHRONIC UREMICS. Pediatr Res 18 (Suppl 4), 365 (1984). https://doi.org/10.1203/00006450-198404001-01635
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DOI: https://doi.org/10.1203/00006450-198404001-01635