The significance of dietary
arginine deficiency is often unrecognized since growth and
nitrogen balance are generally positive. However, inadequate intakes of dietary
arginine are typically associated with dramatic alterations in intermediary metabolism in mammals. Most of the symptoms that develop following
arginine deprivation can largely be accounted for by a decreased efficiency of
ammonia detoxification. However, species differences in the metabolic aberrations associated with
arginine deficiency are clearly evident. Therefore, selected animals fed an
arginine-deficient diet may serve as a useful model for the study of chronic
hyperammonemia. In rats, mice, hamsters, guinea pigs and rabbits, the excretion of citric and
orotic acid is a sensitive
indicator of
arginine availability. Increased
orotic acid production is reduced or prevented by inclusion of the
urea cycle intermediates
arginine,
citrulline or
ornithine. However, growth in the rat is stimulated only when
arginine or
citrulline are included in the diet. Increased orotic biosynthesis is observed with increasing
ammonia concentrations in rat, mouse and human liver and is reduced by in vitro
arginine supplementation. The fatty infiltration of the rat fed an
arginine-deficient diet is associated with changes in the ratio of
purine to
pyrimidine bases and is corrected by the dietary addition of
adenine. The
arginine-deficient rat should serve as a model for examining the dynamic interrelationship of the
urea cycle with
pyrimidine and
purine biosynthesis.