The transport of L-leucine into the brain of the rat in vivo : saturable and non-saturable components of influx

Abstract

The influx of L-leucine into the brain was measured under normal conditions, and also when its concentration in the circulation was progressively increased. The transport system carrying L-leucine into the brain could be saturated, but the results only conformed to Michaelis kinetics if a nonsaturable component was first subtracted from the observed influx data. The proportion of the total influx due to this non-saturable component was small, but it increased as the concentration of leucine in the blood was raised above the normal level. The saturable component of the influx of leucine could be inhibited by raising the concentration of L-valine in the blood, but the influx of leucine into the brain could not be reduced to zero. The residual influx of leucine in the presence of the inhibitor was in part, due to leucine competing with the inhibitor, valine, for the shared carrier, but it was also in part due to the non-saturable component of leucine influx, which is unaffected by the inhibitor. Thus there are two components in the influx of leucine into the brain: a major component, which is a carrier-mediated transport process, and a minor component which is non-saturable. The possibility of a nonsaturable component of the transport of amino acids into the brain has not previously been considered. The non-saturable component may be due to diffusion through the cerebral capillaries in small regions of the brain where the endothelium is permeable; osmotic effects may also contribute. The findings may be of importance in the treatment of aminoacidaemias.