Induction in rats of lysine imbalance by dietary homoarginine

The use of dietary homoarginine (HA) to produce a lysine imbalance was examined in young rats. HA, a basic amino acid analogue, was shown earlier to compete with lysine for transport across the blood-brain barrier. Feeding a diet limiting in lysine and containing HA reduced food intake and growth; increasing dietary lysine content lessened these effects. A 3-fold increase in dietary lysine caused 10, 4, 20 and 50-fold increases in lysine concentrations in plasma, brain, liver and muscle, respectively, and reductions in ornithine concentration of brain and liver and in arginine concentration of brain. HA increased lysine levels in plasma, liver and muscle of rats fed the lysine-limiting control diet, but lysine concentrations were reduced by HA when dietary lysine was high. HA invariably lowered concentrations of lysine, ornithine and arginine in brain and ornithine concentrations in plasma and muscle. Brain concentrations of small and large neutral amino acids were unchanged by HA; an exception was glycine, which was high in the brains of rats fed HA. The HA-associated, selective reductions in levels of each basic amino acid in brain in the ratios of these concentrations to those in plasma support the concept that effects of an amino acid imbalance involve competition for amino acid entry into the brain from the blood.