TRYPTOPHAN TRANSPORT THROUGH THE BLOOD-BRAIN-BARRIER - INVIVO MEASUREMENT OF FREE AND ALBUMIN-BOUND AMINO-ACID

The principles of the competitive ligand binding assay have been extended to the in vivo state to study the competition for tryptophan binding between albumin and the tryptophan transport system localized in the brain capillary wall, i.e., the blood-brain barrier (BBB). Based on the concentration of albumin (1.4 mM) which yields 50% inhibition of BBB tryptophan transport, the dissociation constant of tryptophan binding to albumin (KD = 0.13 mM), and the affinity constant of the BBB tryptophan transport system (KM = 0.19 mM), the apparent binding capacity of the BBB (1.9 mM), may be calculated. The high apparent binding capacity of the BBB enables the capillary transport system to compete with albumin for tryptophan binding; the inhibition of albumin binding by the carrier increases the fraction of tryptophan that is free in vivo to values greater than the fraction that is free in vitro. Depending on physiological changes in KM (e.g., due to plasma amino acid competition) or KD (due to plasma free fatty acid), the apparent free fraction of tryptophan in vivo may approximate either one of two extremes, i.e., the in vitro free fraction or the total tryptophan. © 1979.