270 K. SCHREIER 
found to be increased in several cases of uremia®?:1°7, A hypoaminoacidemia is present 
in the acute stage of nephrotic syndrome? 1°, Only thriving infants, after recovery 
from severe malnutrition, show a similar decrease of the amino acids in blood. 
The metabolism and the handling of the aromatic amino acids during the post-natal 
period deserves a somewhat detailed discussion. In 1941 LEVINE et al." had detected, 
that prematures on a protein-rich diet lacking ascorbic acid excreted breakdown 
products of phenylalanine and tyrosine in considerable amounts. By loading of these 
infants with one or both amino acids the tyrosyluria could be greatly increased. 
SEALOCK AND SILBERSTEIN' had made corresponding observations on guinea-pigs 
with scurvy (1940). In 1go01 SToKvis!"!? observed a darkening of the urine of scorbutic 
human beings. In the meantime several teams have studied the problems of the 
influence of vitamin C on the handling of amino acids in the kidney and particularly 
on the metabolism of aromatic amino acids#43-6, 
The addition of ascorbic acid to the diet resulted always in the disappearance of 
p-hydroxyphenylpyruvic acid and related compounds It also was observed that in 
scorbutic animals and prematures pteroylglutamic acid was able to decrease the tyro- 
syluria4?—19, Furthermore, ACTH decreased the excretion of aromatic keto acids: 12, 
The mode of action of folic acid and ACTH is still obscure. The inconsistent effect 
may be due to an augmented non-specific protein synthesis or an influence on the 
synthesis of a specific apo-enzyme. Initially it was assumed that the oxidation of p-hy- 
droxyphenylpyruvate requires ascorbic acid as an essential cofactor!!*. The fact that 
vitamin C can be replaced by substances like dichlorophenylindophenol!” supports 
the interpretation that these compounds provide an appropriate oxidation—reduction 
potential required for activity of the p-hydroxyphenylalanine oxidase. 
The studies of KRETCHMER and his team?*, #4 cast a new light on the difficulties 
which prematures experience with the metabolism of tyrosine. They showed that the 
activity of the tyrosine-oxidizing system, the tyrosine transaminase and phenyl- 
alanine hydroxylase in the liver of prematures has only 1/,)—'/3_5 of the adult organ 
activity. The same is true for fetal rats. The 7m vitro addition of large amounts of 
ascorbic acid had no stimulatory influence on the tyrosine oxidizing enzyme system. 
It seems likely that the apoenzyme itself is lacking. 
p-Hydroxyphenylpyruvate oxidase on the other hand seems to be present in fairly 
great amounts in tissue of premature and fetal rodents but the enzyme requires very 
large amounts of ascorbic acid for activation. The ascorbic acid might be necessary 
to remove an inhibitor of the enzyme!’. Phenylalanine hydroxylase consists of two 
fractions, of which one (I) is missing in immature liver (see also ref. 125). 
The changes of tyrosine and phenylalanine metabolism in prematures differ there- 
fore from those of the scorbutic adult. The activities of the individual enzymes 
maturate with different speed. Tyrosine transaminase, for example, is active soon 
after birth, producing p-hydroxyphenylpyruvate which accumulates due to the 
shortage of ascorbic acid thus leading to tyrosyluria. According to AURICCHIO et 
al.!*° some enzymes of tryptophane turnover also are lacking or insufficiently active 
in the post-natal period. Besides these acquired anomalies in the turnover of aromatic 
amino acids MEpEs!27, FELrx ef al28 and SAKAI AND KiTAGAWwaA!®9 have found 
changes which some include with the inborn errors of metabolism. In my opinion, 
there is no convincing evidence for an inborn lack of an enzyme in “tyrosinosis”’. 
Bioxam?* has found an increased excretion of tyrosine metabolites in apparently 
References p. 279/283 
