AMINO ACID TRANSPORT INTO CELLS 529 
uptake operates occur by diffusion or by other processes having much the same 
rate for every amino acid, as is usually assumed; but not if exodus occurs through 
mediation by a second site for which a second separate order of affinities applies. 
This second site could of course be an entirely distinct one rather than a modified 
form of the active transport site. In that event we would need to assume that its 
role in exodus is predominant only because our observations are usually made at 
high cellular gradients, causing an asymmetric use of this site for exodus, at the 
steady state just balancing the operation of the active transport site for entry. 
Apparent inconsistencies between the order of affinity and the order of the extent 
of accumulation already can be found if we examine published work. 
In 1952 we showed that the extents of uptake by the Ehrlich cell of the p- and 
L-forms of several amino acids (not including alanine), although generally pre- 
ferring the L-form, are remarkably similar!. Subsequently PAINE AND HEINZ? found 
much larger differences between the D- and L-forms in their effectiveness in inhibiting 
the uptake of glycine. Phenylalanine and histidine were studied in both investigations 
and gave highly divergent results by the two methods. Presumably the comparisons 
by the two methods ought to be made simultaneously before the inconsistency is 
taken to support a double set of affinities. 
In exploring for inconsistency in the affinity series, let us first look at how a 
group of amino acids arrange themselves as to affinity for transport into mature 
human erythrocytes. Although rather typical ability to accumulate amino acids is 
shown by nucleated erythrocytes? and at the reticulocyte stage’, this ability for 
uphill transport has largely been lost on the maturation of these cells. Some amino 
acids, such as glycine, appear endogenously in erythrocytes at levels apparently 
somewhat higher than those in the plasma*, but when added in the labeled form to 
whole heparinized blood, the isotope in the instances so far studied is only very 
slightly accumulated into cells, approaching distribution ratios of approx. I.I on a 
water basis®. These cells probably offer us the best chance to find a simple straight- 
TABLE I 
DISTRIBUTION RATIOS OF AMINO ACIDS, ON A WATER BASIS, BETWEEN RED BLOOD CELLS 
AND PLASMA REACHED IN VARIOUS INTERVALS OF TIME AT 37> 
From WINTER AND CHRISTENSEN?. 
Amino acid 30 min go min 120 min 150 min 240 min 
Glycine 0.26 0.51 0.72 
Sarcosine 0.24 0.47 0.60 
L-Alanine 0.42 (25 min) 0.54 0.74 0.89 
p-Alanine 0.24 (25 min) 0.50 0.62 
a-Methylalanine 0.20 0.35 0.38 0.60 
a-CF,-alanine 0.60 0.70 
L-Proline 0.78 0.95 0.99 
L-Isovaline 0.39 0.77 0.99 
D-Isovaline 0.27 0.56 0.86 
L-Valine 1.01 1.07 1.04 
L-Leucine 1.07 1.05 1.08 
pL-Norleucine 1.05 OF, 1.05 
Cycloleucine 0.96 1.10 
References p. 538 
