699 INTRACELLULAR AMINO ACID LEVELS AS PRE- DICTORS OF PROTEIN SYNTHESIS IN MAN

Abstract

The relation of protein synthesis (PS), a functional expression of amino acid (AA) balance, to the concurrent intracellular (IC) and plasma (P) concentrations of AA is uncertain. We studied 29 normal young adults & 63 neonates 27-44 weeks post-conceptual age, using the circulating neutrophil (LEUK) as the cell model. PS (³H-LEU incorp, pmoles/hr/mg DNA) in the LEUK, 19 AA's (HPLC, fluorometric detection, nmoles/ml) in both LEUK & P, and cell water content (dry weight-“trapped” water by ¹⁴C-inulin) were quantified. In infants, PS was inversely related to birthweight (BWT) & gestational age (GA) (PS = 9265 - 1.2 BWTg -66.35 GA wks;. p=0.0001). With the exception of VAL, CIT, GLN all the ICAA were higher than in P. HIS, ASP, TYR & ORN were the only significant (< .05) self-correlations between 1C & PAA in infants; THR & ILE, in adults. Stepwise multiple regression (MR) was used to identify the set of AA's accounting for the greatest proportion of the variance (R²) in PS. The sets of AA selected by the program were: for PAA in infants, ILE & ALA (R²=0.11, p=0.04); for adults, ASP, GLY, MET (R²)=0.32, p=0.009). For ICAA in infants, LEU, MET, HIS, LYS, GLY, ALA (R²=0.32, p= 0.001); for adults, LEU, MET, HIS, ILE, PHE (R²=0.54, p=0.002). By futher MR analysis, levels of each ICAA predictor of PS in infants & adults was found to be predicted by a different set of PAA's, (e.g., for adults, IC-LEU predicted by P-THR, CIT, VAL, HIS, R²=0.60, p=0.0001). We conclude that: (1) the level of PS can be predicted by a specific set of ICAA's better than by any set of PAA's. (2) The levels of the ICAA predictors of PS can then be predicted by specific, but different, sets of PAA's. These data suggest a possible practical means to modulate cell PS indirectly via ICAA concentrations by altering selected PAA.

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