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I. PERMEABILITY AND AMINO ACID TRANSPORT 
ON THE MECHANISM OF AMINO ACID TRANSPORT INTO CELLS 
HALVOR N. CHRISTENSEN, HITOSHI AKEDO, DALE L. OXENDER 
AND CHARLES G. WINTER 
Department of Biological Chemistry, The University of Michigan, Ann Arbor, 
Mich. (U.S.A.) 
We intend in this presentation to consider some evidence bearing on the nature of 
the process by which amino acids are transported into cells. In selecting this em- 
phasis we donot mean to disregard the unifying interest in the biological meaning 
of the free amino acids of the cell, around which this symposium is organized. Rather 
we hope whatever assistance we can give with that theme can be offered throughout 
the conference, so that we can reserve the present opportunity for directing your 
attention to the challenging problem of mechanism. 
The picture of amino acid transport that has so far emerged for most cells divides 
the amino acids into at least three classes, the neutral, the anionic and the cationic. 
Competitive effects across these class lines are rarely seen and, as far as we are 
aware, not well documented. This division may well arise from the presence of 
three distinct types of transport sites, one for each of these classes. Or instead, the 
charged amino acids may not be able to approach the site for neutral amino acid 
transport because of repulsion by a nearby charged group. In passing we can com- 
ment that we have recently approached this question by synthesizing the new 
amino acid, pL-trifluoromethylalanine: 
la 
CHes (iCOOn 
With remarkable values of 0.5 and 5.94, respectively, for the p&, values of the 
carboxyl and amino groups, this amino acid is monocarboxylic and yet at pH 7.4 
anionic. In various systems it inhibits the transport of neither neutral nor anionic 
amino acids; up to the present we do not know if it even has a mediated transport. 
We can not yet interpret this finding to exclude the possibility that dicarboxylic 
amino acids do use sites differing from those used by neutral amino acids only in 
the presence of a negative charge barrier; this new amino acid has such a strong 
carboxylic dissociation that conceivably the carboxyl group fails to hydrogen-bond 
to the usual bonding points, thereby explaining the absence of interaction with 
ordinary amino acid transport sites. 
My main concern today, however, is with the neutral group of amino acids, and 
with what we may learn by considering interactions in their transport. Questions 
at issue are whether two- or three-point attachment occurs in their transport, and 
References p. 538 
