The shunt pathway of mevalonate metabolism in the isolated perfused rat kidney.
The shunt pathway of mevalonate metabolism (Edmond, J., and Popják, G. (1974) J. Biol. Chem. 249, 66-71) has been studied in isolated kidneys from rats perfused with physiological concentrations of variously labeled [14C]- and [3H]mevalonates. The rate of operation of the shunt pathway was quantified by the production of either 14CO2 or 3H2O from the tracers. The measured rates of 14CO2 production from [14C] mevalonate were converted to rates of mitochondrial acetyl-CoA production by methods which take into account underestimations of metabolic rates derived from 14CO2 production. We have shown that the sex difference in renal shunting of mevalonate (Wiley, M. H., Howton, M. M., and Siperstein, M. D. (1979) J. Biol. Chem. 254, 837-842) occurs at physiological levels of substrate. The shunt pathway diverts up to 17% of the flux of mevalonate entering the cholesterol synthesis pathway in the kidney. It may, therefore, play a role in the long term regulation of cholesterol synthesis in this organ, as had been hypothesized by Edmond and Popják.
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism*; D008954:Models, Biological; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics
D000105:Acetyl Coenzyme A; D008798:Mevalonic Acid