340 E. ROBERTS AND D. G. SIMONSEN 
blood, liver and kidneys of severely vitamin A-deficient rats and pair-fed controls. 
There was no effect of the deficiency on the content of 12 of the constituents. However, 
in blood and the two tissues examined there were significant increases in contents 
of tyrosine and phenylalanine and decreases in threonine in the deficient animals. 
Although the significance of the specific changes is not clear, these results serve to 
show that a deficiency of a dietary essential sufficiently severe to cause anorexia and 
loss in weight may result in relatively small changes in distribution of free amino 
acids. 
Changes in tissue amino acids in ammonia intoxication 
Ammonia intoxication produces remarkably few changes in amino acids of poisoned 
animals. In an acute study LDgg., doses of ammonium acetate (10.8 mmoles/kg) 
were injected into young rats and at death (approx. 15 min), quantitative paper- 
chromatographic determinations were made of alcohol extractable amino acids in 
blood, kidney, muscle, liver, heart, spleen, pancreas, liver and testes** and were 
compared with those from suitable controls. In the liver significant changes were 
found only in aspartic acid (1200%% increase) and alanine (500° increase) contents 
of the 18 constituents detected. The only change noted in the other tissues studied 
Was an increase in glutamine in muscle, brain and testes. Smaller doses of ammonium 
chloride (3.7 mmoles/kg) doubled levels of glutamine in the brains of injected rats®. 
In dogs receiving bilateral carotid infusion of lactate—Ringer’s solution containing 
1% ammonium hydroxide the only significant change found in cerebral free amino 
acids was an increasing content of glutamine with the time of infusion®. Dogs in 
which coma was produced by rapid infusion of the ammonium salt showed virtually 
identical patterns with those of controls. The above results, together with the demon- 
stration of an extremely rapid conversion of intracerebrally administered L-[U-“C]- 
glutamic acid to glutamine in mice®, are compatible with the interpretation that in 
brain there is an extremely rapid incorporation of ammonia into the amide group 
of glutamine 77 vivo by the known synthetic pathway involving glutamic acid, 
ammonia and adenosine triphosphate, by an enzyme known to be at a high level in 
brain. In no case was there found to be a decrease in the content of glutamic acid. 
Although it appears likely that the accumulation of glutamine occurs because the 
combined rates of degradation and exit of glutamine from brain are exceeded by the 
rate of formation when the blood level of ammonia is high, the possibility must be 
considered that inhibition of some normal pathway of glutamine utilization or 
breakdown may also contribute to the elevated levels of cerebral glutamine. 
Influence of hormonal changes on free amino acids 
An extensive series of studies was performed in which comparisons were made of 
amino acids of tissues of normal rats with littermate controls in which there was 
experimental impairment of function or removal of one of the major endocrine 
glands. The results to be reported further confirm the remarkable stability of the 
free amino patterns in tissues of an organism in which great physiological changes 
have been produced and a variety of adaptations are taking place (see refs. 66 and 
67 for pertinent references). 
References p. 348/349 
