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Journal of Lipid Research, Vol. 23, 1317-1320, December 1982
Copyright © 1982 by Lipid Research, Inc.

Evidence for an underestimation of the shunt pathway of mevalonate metabolism in slices of livers and kidneys from fasted rats and rats in diabetic ketosis

Paul S. Brady , William C. Schumann , Seiji Ohgaku , Richard F. Scofield , and Bernard R. Landau

Departments of Medicine and Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106

Yields of ¹⁴CO₂ from [2-¹⁴C]mevalonate and [5-¹⁴C]mevalonate have been used by others to estimate the activity of the non-sterol-forming pathway, also called the mevalonate shunt pathway, and yields of ¹⁴C in sterols have been used to estimate the activity of the sterol-forming pathway. Both these pathways operate following the conversion of carbon 1 of mevalonate to CO₂. The estimations of the shunt pathway contribution are dependent upon the fractions of carbons 2 and 5 of mevalonate that are oxidized to CO₂ in the Krebs cycle after leaving the pathway. Unless all of carbons 2 and 5 are oxidized to CO₂, the estimates are minimal. The metabolism of mevalonate has now been examined in slices of livers and kidneys from fasted rats and rats in diabetic ketosis. Yields of ¹⁴CO₂ from [1-¹⁴C]mevalonate are used as the measure of the contributions of all the pathways by which carbon 1 of mevalonate is converted to CO₂. Yields of ³H-labeled nonsaponifiable lipids from [5-³H]mevalonate are used as the measure of the sterol-forming pathway. The differences in these yields are then taken as the measure of the non-sterol-forming pathway or pathways. Yields of ¹⁴CO₂ from [1-¹⁴C]mevalonate markedly exceeded the sum of the yields of ¹⁴C in CO₂ and nonsaponifiable lipids from either [2-¹⁴C]mevalonate or [5-¹⁴C]mevalonate. Therefore, in liver and kidney, under the conditions of this study, either one or more pathways other than the shunt pathway, by which mevalonate can be metabolized to other than sterols, is operative to a marked degree, or estimates of the shunt pathway's contributions as judged by yields of ¹⁴CO₂ from [2-¹⁴C]mevalonate and [5-¹⁴C]mevalonate are significantly underestimated.—Brady, P. S., W. C. Schumann, S. Ohgaku, R. F. Scofield, and B. R. Landau. Evidence for an underestimation of the shunt pathway of mevalonate metabolism in slices of livers and kidneys from fasted rats and rats in diabetic ketosis.

Supplementary key words mevalonate shunt pathway • sterols • kidney • liver

Submitted on February 23, 1982
Revised on July 21, 1982

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