Sterol synthesis and CO2 production from mevalonate in calves

Nonruminating male Holstein calves were fed a reconstituted milk containing 11.7% nonfat-dried-milk solids and 3.5% beef tallow. Calves were slaughtered at 17 weeks of age. Samples of perirenal adipose tissue, liver, muscle, small intestine, kidney cortex, and kidney medulla were assayed in vitro for sterol synthesis and production of (14)CO(2) from [2-(14)C]mevalonate. Of the tissues tested, adipose tissue and kidney medulla produced nonsaponified lipids at the greatest rates; kidney cortex and liver at half the rate of adipose tissue; muscle and jejunum at one-eighth the rate of adipose tissue; and ileum at a negligible rate. The amount of (14)C in squalene, lanosterol, and cholesterol of the nonsaponified lipids of each tissue was determined by thin-layer chromatography. Proportions of (14)C in cholesterol to (14)C in total nonsaponified lipids ranged from 30% to 59%; squalene, from 5% to 27%; and lanosterol, from 11% to 59% of the total nonsaponified lipids present. The rate of CO(2) production by the "trans-methylglutaconate shunt of mevalonate metabolism" was determined. Kidney cortex displayed the greatest shunt activity, producing 15-80-fold more CO(2) than any other tissue tested. Ileum, jejunum, skeletal muscle, and kidney medulla had similar shunt activities; liver sections had less shunt activity, and no shunt activity was detected in adipose tissue. These data reveal a shunt for mevalonate utilization that does not lead to sterols and also show that the kidney is important in the sterol and nonsterol metabolism of mevalonate.