The effect of a histidine-excess diet on cholesterol synthesis and degradation in rats.

Feeding a diet high in excess histidine (5% L-histidine) resulted in hypercholesterolemia and enlargement of the liver in rats. To clarify the mechanism of the hypercholesterolemia, cholesterol synthesis and degradation were followed. We found that hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in histidine-excess diet rats was significantly higher than in rats fed a basal diet. Incorporation of [3H] water into cholesterol of liver slices from rats fed the histidine-excess diet was higher than incorporation into liver slices from rats fed the basal diet (expressed per liver per 100 g body weight). In vivo incorporation of [3H] water into hepatic cholesterol was also higher, but the incorporation into cholesterol of the small intestine was lower in histidine-fed rats than in rats fed the basal diet (expressed per liver per 100 g body weight). Hepatic cholesterol 7 alpha-hydroxylase activity was similar in both groups. The data suggest that the hypercholesterolemia caused by histidine-excess diet appears to be due to the stimulation of cholesterol synthesis in the liver.