Kinetics of tryptophan transport across the blood-brain barrier

Abstract

The transport of tryptophan across the blood-brain barrier in vivo has been analyzed kinetically to assess the influence upon it not only of the concentration of tryptophan in the blood plasma, but also of the inhibitory effect of fourteen other amino acids normally present in the circulation. The transport of tryptophan into the brain conforms to the equations of enzyme kinetics with competitive inhibition, provided appropriate modifications are made to take account of a non-saturable component (possibly passive diffusion) in the transport, and of the normal presence in the blood of other amino acids which act as competitive inhibitors. The inhibitor constant has been evaluated for each amino acid and in many cases it corresponds fairly closely with the Michaelis saturation constant for that amino acid, suggesting that tryptophan and these inhibitors share a common transport carrier. The implications of the kinetic analysis are considered for hormonal and metabolic disturbances which change the proportions of amino acids in the blood. The effect of an increase in competitive inhibition due to raised levels of amino acids is to make the tryptophan influx more directly dependent upon the level of tryptophan in the blood.