Activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase does not respond to ubiquinone uptake in cultured cells.
The cellular content of ubiquinone was increased approx. 10-fold by incubation of neuroblastoma cells in medium containing exogenous ubiquinone. Under these conditions the activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, assayed after preincubation of cell homogenates with or without fluoride, was not suppressed. Similar results were obtained with human skin fibroblast cultures to which free ubiquinone or low-density lipoprotein-ubiquinone complex had been added. Consistent with the lack of suppression of HMG-CoA reductase, the rate of incorporation of [1-14C] acetate into ubiquinone was not diminished in cells exposed to exogenous ubiquinone. Measurements of [3H]mevalonolactone incorporation into cellular ubiquinones indicated that exogenous ubiquinone did not affect ubiquinone synthesis at a point in the pathway distal to the formation of mevalonate. The results suggest that cultured mammalian cells lack an end-product 'feedback' mechanism for regulation of HMG-CoA reductase in response to ubiquinone uptake.
Division of Pediatric Neurology, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
W A
WA
Maltese
J R
JR
Aprille
R A
RA
Green
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D014451:Ubiquinone / Q000096:biosynthesis / Q000493:pharmacokinetics* / Q000494:pharmacology
D001798:Blood Proteins; D014451:Ubiquinone; D006903:Hydroxymethylglutaryl CoA Reductases; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent