FREE AMINO ACIDS OF BLOOD AND URINE 241 
case, another question arises: is proline so completely reabsorbed that not a trace 
is to be found in normal urine, even when such a high resolution-power instrument as 
the automatic recording ion-exchange chromatographic machine is used, or does it 
not pass into the glomerular filtrate? It must be recalled here that the use of the auto- 
matic recording procedure has led to the recognition of a faint trace of hydroxypro- 
line in normal human fasting plasma" heretofore not detected by any other analytical 
procedure. 
The clearance concept, as applied to amino acids, relies on the assumption that 
they all pass equally easily into the glomerular filtrate and are present there at 
approximately the same concentration as in plasma. For most cf the amino acids 
this might be the case, but nothing whatever tells that their concentration in the 
glomerular filtrate is not significantly different from what it isin the plasma. A Donnan 
effect in the distribution of amino acids between plasma and glomerular filtrate 
does not seem to be taken into account although amino acids are electrolytes. Except 
in one instance, it is not known if protein binding of amino acids occurs in the plasma, 
in which case the filterability of these solutes would be reduced to some yet unknown 
extent. 
It must be born in mind that what is called free amino acid concentration in the 
plasma are values determined on deproteinization filtrates, a procedure which 
might well be able to break weak bonds between protein and amino acids if such 
a protein binding does really occur. Protein binding seems to be a reversible reaction, 
determined by the specific nature of the solute, by the concentration of the solute, 
by the concentration of protein as well as by H* concentration, temperature or 
other factors. 
Up to now, only McMEenamy et al.3!, 4° claim that there is evidence for such a 
protein binding, especially in the case of tryptophane which, they say, is largely 
bound to albumin. 
The presence and extent of protein binding of amino acid should be determined 
by ultrafiltration experiments before calculating the filtered load of such solutes. 
Whatever its response, such an experiment would be worth carrying out by means 
of reliable analytical methods. It will presumably show that some of the amino 
acids do not pass freely through the dialyzing membrane, as suggested by a former 
study done by McMENamy ef al.4°. As it is, the clearance concept applied to renal 
handling of free amino acids has already proved useful since it is used as the basis 
for interpretation of the mechanism of abnormal aminoaciduria and has led to 
DEN?’s classification of abnormal types of aminoaciduria in disease’. It has also 
led to interpretation of some non-pathological situation such as the hyperamino- 
aciduria that occurs in the course of normal pregnancy as a result of increased 
glomerular filtration rate induced by hormonal hyperactivities®. 
However, it seems that more knowledge has still to be gained, especially in regard 
toaminoacid glomerular filtration and the very nature of the reabsorption mechanism, 
before full understanding of the process will be achieved. 
BLOOD POOLS OF FREE AMINO ACIDS 
Animal tissues contain much greater amounts of free amino acids than the corre- 
sponding blood plasma. This has been demonstrated by TaLLAn et al. who published 
References p. 261/262 
