Interchange of Amino Acids between Blood and Tissues

During digestion the amino acid content of the blood rose about 20 per cent, as the blood perfused the intestines, and that the greater part of the absorbed amino acids was removed by the liver. In return, the liver poured into the blood of the hepatic vein an amount of urea nitrogen that had been taken up. One could watch the work of the liver in taking up the amino acids and destroying them, turning their nitrogenous parts into urea for excretion by the kidneys. Unreasonable and wasteful though it seems, a large part of the amino acids absorbed from the intestine appears to be captured and destroyed by the liver, and never to have a chance to reach and nourish the other tissues. Other experiments, showed that the liver did not get all the absorbed amino acids, but that some escaped, and could be absorbed by other tissues. It was found that even in the fasting animal the amino acid concentration in the tissues was about 10 times as great as in the blood plasma, viz., about 40 to 60 mg. of amino acid nitrogen per 100 grams of tissue, compared with 5 mg. per 100 grams of plasma. When amino acids were injected into the circulation they were quickly taken from the blood by the tissues, where the amino acid contents might be increased to 2 or 3-fold their former values.

In one experiment the amino nitrogen of the liver rose to 150 mg. per 100 grams; in the muscles the increase was never so great. During the next three hours the amino acids in the muscles and kidneys remained practically unchanged, but the amino acids in the liver fell almost back to their original level, and an equivalent of urea nitrogen appeared in the circulation. Fate of Amino Acids in the Liver. The evidence in these experiments, that the liver is the organ where urea formation takes place, supported an old but much contested hypothesis that the liver is the only organ that forms urea. The removal of the livers led to an accumulation of amino acids in the blood, and entirely stopped the formation of urea. Another vicissitude of the amino acids which the work of Mann and his colleagues located in the liver is transformation into glucose. When protein was catabolized by dogs made totally diabetic by phloridizin poisoning, about 60 grams of glucose were formed and excreted from each 100 grams of protein catabolized. When certain amino acids were fed their carbon was partly or entirely turned into glucose when their nitrogen was turned into urea. No glucose formation from proteins or amino acids occurred when the liver was excluded. Furthermore, the acceleration of the body's heat production that occurs during assimilation of protein digestion products was shown not to occur when the liver was excluded. This accelerated heat production, called the "specific dynamic action," apparently either represents energy produced by the reactions which the amino acids undergo in the liver, or is caused by other reactions in the cells which are stimulated by the presence of products formed in the liver. Such substances must be other than the urea and glucose, for neither of these causes the observed amount of heat acceleration. Not all the treatment met by the amino acids in the liver is destructive.

During periods of heavy protein feeding the body stores considerable amounts of protein in the liver and, in less amounts per gram of tissue, in the other tissues. The reserve protein seems to be different from the structural proteins of the tissues. In the liver it can in fact be differentiated with the microscope by its droplet structure in the cells. Functionally it is characterized by the readiness with which it is metabolized at the onset of starvation, and with which it is used to replace blood proteins depleted by hemorrhage. The liver also appears to be the place where plasma fibrin and albumin are formed. It was demonstrated hundred years ago that injury of the liver retarded or prevented formation of fibrin. The liver is essential also for the formation of the albumin of the plasma. These proteins are presumably formed from free or combined amino acids taken out of the blood by the liver.