Possible involvement of 3-hydroxymethylglutaryl-CoA reductase in determining the side-chain length of ubiquinone in rat heart.
The biosynthetic mechanism for determining the side-chain length of ubiquinone in rat heart mitochondria was investigated. The biosynthesis of nonaprenyl ubiquinone (UQ-9) and decaprenyl ubiquinone (UQ-10) in the mitochondria from rat hearts previously perfused with mevalonolactone was accelerated depending on the concentration of mevalonolactone. Furthermore the synthesis ratio between UQ-10 and UQ-9 (UQ-10/UQ-9) increased in accordance with the increasing concentration of mevalonolactone used. In addition, an enhancement of the synthesis ratio (UQ-10/UQ-9) was observed when the rats were treated with isoproterenol to increase the activity of 3-hydroxymethylglutaryl-CoA (HMG-CoA) reductase, a rate-limiting enzyme which forms mevalonate. Moreover, the addition of isopentenyl pyrophosphate, which is a metabolite of mevalonate, elevated the synthetic ratios UQ-10/UQ-9 in intact mitochondria and decaprenyl pyrophosphate/solanesyl pyrophosphate in the partially purified polyprenyl pyrophosphate synthetase from rat heart. These results suggest that the HMG-CoA reductase could be involved as a determining factor of the side-chain length of ubiquinone in rat heart.
Shimizu
S
S
Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Yamamoto
T
T
Sugawara
H
H
Kawahara
Y
Y
Momose
K
K
D000818:Animals; D011756:Diphosphates / Q000378:metabolism; D045782:Hemiterpenes; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007460:Iodoacetamide / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013729:Terpenes / Q000378:metabolism; D014451:Ubiquinone / Q000096:biosynthesis / Q000378:metabolism*
C003188:3-polyprenyl-4-hydroxybenzoate; D011756:Diphosphates; D045782:Hemiterpenes; D009943:Organophosphorus Compounds; D011106:Polyisoprenyl Phosphates; D013729:Terpenes; D014451:Ubiquinone; C004809:isopentenyl pyrophosphate; C063778:solanesyl pyrophosphate; C015367:mevalonolactone; D006903:Hydroxymethylglutaryl CoA Reductases; D007545:Isoproterenol; D008798:Mevalonic Acid; D007460:Iodoacetamide