Supplementation of a closed formula, cereal based stock diet with excess L-histidine at a 5% or 8% level for 4 days reduced growth and induced hepatomegaly and an increase in plasma cholesterole levels in weanling rats. The enlargement of the liver was in part due to glycogen accumulation; plasma glucose concentration was unchanged. Feeding four different amino acids (L-phenylalanine, L-glutamic acid, glycine and L-tryptophan), at levels which caused reduction of growth comparable to the 5% and 8% L-histidine supplementation, did not effect liver weight or plasma cholesterol levels. L-Threonine added, at a 2% level, to the 8% L-histidine diet did not alleviate any of the histidine effects. Rats fed a diet containing 5% urocanic acid, the first metabolite of the histidine degradative pathway, grew at a normal rate but had higher plasma cholesterol levels compared to rats fed stock diet. When rats fed L-histidine-or urocanic acid-supplemented diets were returned to stock diet, a normal growth rate was resumed immediately and plasma cholesterol levels returned to normal within 6 days. These results suggest that L-histidine and/or urocanic acid induce a hypercholesterolemia which disappears several days after the supplementation ceases.

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A time study of the metabolism of 6,7‐14C‐retinoic acid after intraperitoneal injection of physiological levels (17 μg, 0.39 μc) into vitamin A deficient rats, which had been repleted with retinoic acid for two weeks up to two days before injection, resulted in a rapid metabolism to more polar compounds in the small intestine and its contents and a slower metabolism to primarily different materials in the liver and kidney. The major route of metabolism resulted in the urinary excretion of 60% of the injected dose in 24 to 27 hr. Urinary metabolites of 15‐14C‐retinoic acid were eluted from silicic acid at a similar concentration of solvents as the ring labeled metabolites although only 32% of the injected dose was recovered in 24 hr. Compounds chromatographically similar to the urinary metabolites were observed at various times in the liver, kidney and small intestine plus contents in addition to retinoic acid and other metabolites. The relative amounts of the metabolites in the different tissues studied varied as a function of the tissue and the time of analysis after injection. Most of the radioactivity from all tissues was extractable into methanol. A liver subcellular distribution of the radioactivity derived from the intraperitoneal injection of 650 μg of 6,7‐14C‐retinoic acid (25.9 μc) after 3 hr indicated a minimal level of association of radioactivity (150–250 dpm/mg protein) with all fractions and a greater association of radioactivity with the lysosomal‐microsomal fraction (300–350 dpm/mg protein) and the 60–100% ammonium sulfate precipitable (750–800 dpm/mg protein) and 100% ammonium sulfate soluble fractions (422 dpm/mg protein) of the soluble supernatant.