Recognition chemistry of anionic amino acids for hepatocyte transport and for neurotransmittory action compared

Abstract

Comparison of neuronal and non-neuronal membrane transport of, and neuroexcitation by, the dicarboxylic amino acids bring out provocative similarities in structural selectivity, and hence in the strategies for studying them. Parallel anomalies in stereoselectivity show for both phenomena that the recognition sites are indeed chiral, as expected for biological functions, even though both fail in special instances to discriminate between pairs. High and low affinity, or Na+-dependence or Na+-independence, are not fully reliable bases for discriminating receptor sites serving one of these functions. Tolerance of N-methylation of the amino acid serves in discriminating families of recognition sites for both phenomena, as does substitution of the sulfonate or sulfinate for the distal carboxylate group, or other structural changes. Analogs in which the functional groups of aspartate or glutamate are presented in restrained arrays serve for both, although they have so far suggested identity neither of recognition sites for transport and excitation, nor of the events consequent to binding for these two phenomena.