712 Le Ls MILE ER 
Table I also summarizes comparative observations on the oxidation of a group of 
non-essential amino acids which are as extensively oxidized to CO, by non-hepatic 
tissues as by the liver. Figs. 8-11 present some more detailed data on the oxidation 
of 1-[U-4C]glutamic acid and 1-[U-C]alanine. In summary, the experimental 
results here clearly separate the amino acids into two large groups, one group of 
seven essential amino acids which are almost exclusively oxidized by the normal 
liver and another substantial and larger group which contains the amino acids that 
are as avidly oxidized by non-hepatic tissues as by the liver. 
DISCUSSION 
The observations of BOLLMAN, MANN AND MaGATH® on gross changes in the blood 
amino acid level in hepatectomized dogs led some to conclude that the liver was the 
sole site of deamination and presumably of oxidation of amino acids in the mammalian 
organism. Our observations lead to significant modification of this point of view. 
The results we have obtained with [1*C)amino acids more sharply focus attention on 
the group of essential amino acids, excluding leucine, isoleucine and valine, in con- 
nection with experimental and clinical hepatic insufficiency. They make more under- 
standable how hepatic insufficiency may produce the qualitative and quantitative 
changes in the blood amino acid picture®-! described in the literature. Thus, in 
terms of our results, severe hepatic insufficiency connotes inability to handle lysine, 
arginine, histidine, phenylalanine, methionine, tryptophane and threonine. Of this 
group, methionine and phenylalanine and their related derivatives, cysteine and 
tyrosine, have received attention from a variety of observers!’ #3; and it may not 
be entirely fortuitous that the non- hepatic tissues of the rat oxidize phenylalanine 
and methionine to the lowest extent of any of the amino acids. 
60 






50 


Pe CUMULATIVE 
Dose '*c 40 
x dose '4c PERFUSED O—O ee 
lett rae ead eae PERFUSED 
PER HOUR NON- HEPATIC LIVER 0-0 
T UES 
20 ISSUE Qs 20 NON-HEPATIC 
TISSUES 
10 10 
fe) (o) 
lps OMe aS: [> S2ho Raa: 
HOURS HOURS 
Fig. Io. Fig. 11. 
Fig. 10-11. Oxidation of L-[!4C]glutamic acid by the liver compared with non-hepatic tissues. Rat 
liver perfusion (RLP 515). Normal Wistar male (weight, 328 g) as liver donor, liver weight, 7.2 g. 
Dose of 0.5 mg of [U-!@C]glutamic acid (4 wC) mixed with 51 mg L-glutamic acid and 500 mg of 
glucose added to perfusion blood, tg1 ml. Eviscerated surviving rat (EVR-GI-AC-16), Sprague- 
Dawley male (weight, 183 g); dose of t-glutamic acid same as for the perfusion above. 
In general, it becomes clear that the non-hepatic tissues are capable of oxidizing 
amino acids corresponding to approx. 50-65%, of the nitrogen in the average protein. 
In terms of our current knowledge of intermediary amino acid metabolism, the 
production of glutamine in the peripheral tissues serves as a relatively non-toxic 
means of transport of nitrogen to the liver. It is of some interest, we believe, that 
although severe changes in hepatic function incidental to the precancerous state or 
References p. 721 
