LIVER AND AMINO ACID LEVELS IN BLOOD TGS 
to experimental cirrhosis are associated with impairment of capacity to oxidize 
amino acids and to produce urea from amino acids! that the capacity to produce 
urea at a normal rate from glutamine is retained?!®. This is all the more remarkable 
since this occurs even at a time in the development of experimental hepatic insuff- 
ciency when the production of urea from arginine is also obviously impaired. We 
have pointed to this observation in the past!® as one imposing bit of evidence in 
favor of a pathway of urea synthesis other than that conventionally associated 
with the Krebs-Henseleit urea cycle. 
Part 2. Changes in blood amino acid levels seen during tsolated 
liver perfusion studies 
We have previously® summarized our observations pointing to the fact that when 
a complete amino acid mixture is added to the blood in the isolated perfused rat- 
liver system, the normal liver rapidly clears such amino acids from the circulating 
blood. Thus, a test dose consisting of a mixture of all the essential and non-essential 

35.0 7 
or - AAS,NO CHO (5) 
© -~—— AAS, 1.2 GLUCOSE (2) 
30.0 2--- AAS,1,.9 GLUCOSE (3)9 
4-NO SUBSTRATE ADDED (5) 




25.0 4 
BLOOD 
AA-N | 
Mgt. 20° 
15.0+ ° - 
mes = 4 
| 
5.0 1 - . . . . . 
Fig. 12. Changes in blood amino acid concentration during 
pees . . isolated rat-liver perfusion. For detailed explanation, see 
1 2 3 4 
5 
TIME I) PEWS MILLER, BURKE AND HArFT?. 
amino acids whose composition is described in detail elsewhere? is rapidly cleared 
from the blood with an equilibrium value of 14-18 mg, of a-amino acid nitrogen 
being reached at the end of 4-6h (Fig. 12). In order to obtain a more detailed 
picture of the specific amino acid changes occurring during the course of perfusion of 
a complete mixture of amino acids®, we have separated the amino acid from equal 
volumes of plasma taken at zero time and at the end of 5 or 6h of liver perfusion. 
Fig. 13 compares the initial and final chromatograms and reveals that during the 
course of the perfusion, there was a general decrease in the apparent concentration 
of most amino acids. However, there is a striking persistence, if not an actual in- 
crease, in the leucine—isoleucine and valine spots. This latter observation may, per- 
haps, be thought to represent the result of the quantitatively smaller degree of 
oxidation of leucine, isoleucine, and valine as noted previously for the isolated per- 
fused liver. However, it will become apparent from subsequent observations that 
the persistence of, or a real increase in leucine, isoleucine and valine probably results 
from protein breakdown by the liver. In fact, in a liver perfusion (exemplified by 
Fig. 14), where no extra amino acids have been added to the perfusing blood, en- 
hanced leucine—isoleucine spots stand out prominently in chromatograms of the 
References p. 721 
