The acid strength of the amino group as a factor in the transport of amino acids

Abstract

1. 1. Halogen atoms have been introduced on the [beta]-carbons of amino acids in order to dissociate effects on pKa of the amino group on transport, from effects of the hydrophilic or hydrophobic character of the side chain.2. 2. [alpha]-Monofluoromethyl- and [alpha]-trifluoromethylalanine have been synthesized by adaptations of the Strecker synthesis. The pKa of the amino group in these 2 cases was lowered by 1.6 and 4.3 units, respectively, by the introduction of fluorine.3. 3. These fluorine-containing amino acids are resistant to metabolism, and apparently non-toxic. The first shows characteristic biological transport, but in all situations studied, whether in vivo or in vitro, its transport is weaker than for the unfluorinated methylalanine.4. 4. The anionic trifluoromethylalanine gives no evidence of specific mediation in its transport, either by reference to neutral amino acids or to glutamic acid.5. 5. [alpha]-Chloroalanine also has somewhat lower affinity for transport than alanine.6. 6. These results indicate that the charged rather than the uncharged form of the amino group probably participates in amino acid transport.