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Conversion of [2-¹⁴C]Mevalonate into Cholesterol, Lanosterol and Squalene in Copper-Deficient Rats^1,2,

Nutrition Program, Department of Home Economics, Mississippi Agricultural and Forestry Experiment Station, Mississippi State University, Mississippi State, MS 39762

This study was designed to examine the effect of copper deficiency on the conversion of mevalonate into cholesterol in rats. Thirty weanling, male Sprague-Dawley rats were divided into two dietary treatments. The copper-deficient and adequate diets contained 2 and 18 mg Cu/kg of diet, respectively. Feed and water were provided ad libitum. After 8 weeks of treatment, the rats were fasted overnight and then injected with 0.5 µCi of [¹⁴C]mevalonate per 100 g body weight via the femoral vein. Five rats from each treatment were killed after 40, 80 and 120 minutes. In rats fed the copper-deficient diet, the serum free cholesterol concentration was significantly elevated and the serum ester cholesterol concentration appeared to be elevated, but the trend was not significant. The liver free cholesterol concentration appeared to be reduced, but the trend was not significant, and the liver ester cholesterol concentration was significantly reduced in the rats fed the copper-deficient diet. The specific activity (SA) of the total cholesterol of the kidney, and the radioactivity of kidney squalene and lanosterol, were not different between the rats fed the two diets. The liver ester cholesterol SA reached a peak at or before 40 minutes in rats fed the copper-deficient diet. The SA of liver ester cholesterol from the rats fed the copper-adequate diet increased between 40 and 120 minutes. The results suggest that in the rats fed the copper-deficient diet the liver ester cholesterol, newly synthesized from [¹⁴C]mevalonate, was leaving the liver pool at an increased rate. The serum ester cholesterol SA was elevated in rats fed the copper-deficient diet at all times suggesting that the newly synthesized ester cholesterol may be entering the serum pool at an increased rate or leaving the serum pool at a reduced rate or both. This may account for the hypercholesterolemia observed in rats fed the copper-deficient diet.

KEY WORDS: • copper deficiency • hypercholesterolemia • cholesterol metabolism

¹ Aided by funds from the Mississippi Agricultural and Forestry Experiment Station and published as Article Number 4264.

² Presented in part at the annual meeting of the Federation of American Societies for Experimental Biology, Dallas, TX, April 1979.

³ To whom reprint requests should be sent at present address: Dept. of Nutrition & Food Science, University of Arizona, Tucson, AZ 85721.

Manuscript received 30 July 1979.

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