THE EFFECT OF TYROSINE-DEFICIENT TOTAL PARENTERAL-NUTRITION ON THE SYNTHESIS OF DIHYDROXYPHENYLALANINE IN NEURAL TISSUE AND THE ACTIVITIES OF TYROSINE AND BRANCHED-CHAIN AMINOTRANSFERASES

The poor solubility of tyrosine (Tyr) limits the amount of this amino acid in total parenteral nutrition (TPM), In rats maintained on a stan dard pediatric TPN mixture, plasma and brain concentrations of Tyr are reduced to about 25% of the levels in chow-fed controls, To determine whether these low concentrations of Tyr affect the synthesis of catec holamines in neural tissue, the rate-limiting step (conversion of Tyr to dihydroxyphenylalanine [DOPA]) is studied by administering NSD-1015 to block the pyridoxal phosphate (PLP)-dependent decarboxylation of D OPA, However, in TPN rats, plasma concentrations of Tyr are increased by drug treatment. Because brain Tyr is also increased, these and othe r experiments using NSD-1015 clearly overestimate the rate of DOPA syn thesis for drug-free rats on TPN, Nevertheless, in TPN rats, there is less DOPA in the brain in one experiment and less DOPA in the olfactor y bulbs in another, versus control rats, Further examination, of the m etabolic effects of NSD-1015 reveals that the drug also elevates the c oncentration of branched-chain amino acids (BCAAs) in the plasma of TP N rats. These findings result from inhibition by NSD-1015 of the PLP-d ependent aminotransferases that initiate catabolism of Tyr in the live r and BCAAs in the muscle, Despite the pronounced reduction in plasma Tyr, TPN rats showed a marked increase in the activity of hepatic tyr aminotransferase compared with chow-fed controls, Conversely, although TPN elevates BCAA concentrations in plasma, the activity of branched- chain aminotransferase (BCAT) in the heart muscle of TBM rats is not d ifferent from control values. Different values but the same relationsh ips are seen in drug-free rats. Copyright (C) 1998 by W.B. Saunders Co mpany.