HYPERAMMONEMIA-INDUCED DEPLETION OF GLUTAMATE AND BRANCHED-CHAIN AMINO-ACIDS IN MUSCLE AND PLASMA

Background/Aims: Exogenous hyperammonemia is known to decrease the pla sma levels of branched-chain amino acids (BCAA), To investigate whethe r changes in intracellular amino acid concentrations of muscle are ass ociated with and may, at least in part, mediate this effect, experimen ts were carried out on a total of 60 male Wistar rats. Methods: Five g roups were formed in a randomized manner. Group A: no treatment; group s B1 and B2: 2-hour and 6-hour continuous central-venous infusions, re spectively, of sodium salts; groups C1 and C2: 2-hour and 6-hour infus ions of ammonium salts. We obtained venous blood samples and muscle bi opsies. Plasma ammonia, whole blood glucose, serum insulin, blood pH, and amino acids in plasma as well as in the intracellular water of mus cle were measured. Results: As compared with control group A, groups C 1 and C2 displayed a 3.3- and a 4-fold increase, respectively, in the plasma ammonium concentration. Regarding insulin, the ammonium-infused rats were similar to group A but not to the sodium-infused B groups, which had significantly lower insulin concentrations. Administering am monium brought about a decline in BCAA concentrations in plasma after 2 hours and in muscle after 6 hours. The ammonium-induced fall in intr acellular BCAA values was preceded by an increase of glutamine as well as by a decrease of glutamate and alanine in both plasma and muscle. Conclusions: It is pointed out that the inter-group differences in ser um insulin, although possibly accounting for some of the findings, can by no means explain the entire pattern of amino acid concentrations s een after the ammonium infusions. Instead, our results agree-with the hypothesis that hyperammonemia indirectly lowers the plasma levels of BCAA by stimulating glutamine synthesis, thus reducing the intracellul ar glutamate pool, which is likely to be restored, at least in part, b y an intensified BCAA transamination. Clarification is needed as to wh ether carbon skeletons derived from valine and isoleucine additionally contribute to replenishing the glutamate pool.