Differential effect of total food withdrawal and dietary protein restriction on brain content of free histidine in the rat.

Total withdrawal of food from young rats for 72-120 h produced an increase in brain content of free histidine which was less pronounced than the effect of prolonged dietary protein deficiency. The data suggested that the elevated brain content of histidine in both fasting and protein deficiency was due partly to increased plasma level of the amino acid but mainly to diminished plasma concentrations of the neutral amino acids known to share the same transport system across the blood-brain barrier. The results also support the idea that total starvation, and most likely, prolonged caloric restriction, like protein malnutrition, elicit increased formation of histamine in brain since the key regulatory enzyme, L-histidine carboxylase (EC 4.1.1.22) functions at less than maximal efficiency under normal brain levels of histidine. These findings in the rat are probably relevant to the human in view of evidence that the Km of blood-brain barrier neutral amino acid transport in the latter is low and therefore similar to the situation in the rat.