Regulation of the amino acid availability in the developing brain. No physiological significance of amino acid competition in experimental hyperphenylalaninemia.

Chronic experimental hyperphenylalaninemia in suckling rats causes a depletion of amino acids in the blood and in the brain, and an accumulation of amino acids in the peripheral tissues. The amino acid depletion in the blood is greater than that in the brain. The amino acid accumulating potency of all body tissues is increased by the excess of phenylalanine, most pronounced in the gut, least pronounced in the brain. All body tissues compete for the amino acids circulating in the blood. This competition is enhanced in hyperphenylalaninemia. The brain is at a disadvantage in the competition of the various body tissues for the amino acids available from the common pool. Brain tissue is increasingly depleted of amino acids as the accumulation of amino acids in the peripheral tissues is stimulated in hyperphenylalaninemia. The depletion of amino acids in the blood and the simultaneous rise of the free amino acid concentrations in the various developing tissues indicates tissue-specific shifts in the balance between protein synthesis and protein degradation in hyperphenylalaninemia. There is no indication that amino acid competition at the blood-brain barrier contributes importantly to the depletion of amino acids in the brain tissue in hyperphenylalaninemic rats. Instead, brain amino acid pools under in vivo steady-state conditions appear to be primarily regulated by the rate of amino acid utilization by the peripheral tissues.