Regulation of coenzyme Q biosynthesis.
The side-chain moiety of coenzyme Q is synthesized by a trans-prenyltransferase present in microsomes. Condensation of this moiety with the precursor ring takes place in the Golgi system. The enzymes involved, as well as the cytosolic geranylgeranyl-PP synthase, are regulated in an independent fashion. When the size of the farnesyl-PP pool is decreased or increased by employing appropriate inhibitors, the rate of CoQ synthesis is modified accordingly, indicating the dependence of trans-prenyltransferase activity on the level of intracellular substrate concentrations. Administration of peroxisome proliferators elevates CoQ concentrations not only in blood, but also in various tissues. Thus, it may be possible in the future to selectively increase CoQ concentrations in certain organs, without increasing the level of cholesterol.
Appelkvist
E L
EL
Division of Medical Cell Biology, Karolinska Institutet, Huddinge, Sweden.
Aberg
F
F
Guan
Z
Z
Parmryd
I
I
Dallner
G
G
D019883:Alkyl and Aryl Transferases; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D004122:Dimethylallyltranstransferase / Q000378:metabolism; D004286:Dolichols / Q000096:biosynthesis; D004789:Enzyme Activation; D005057:Eukaryotic Cells / Q000378:metabolism; D051231:Farnesyltranstransferase; D006056:Golgi Apparatus / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology; D008798:Mevalonic Acid / Q000378:metabolism*; D008830:Microbodies / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009928:Organ Specificity; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D051381:Rats; D014166:Transferases / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured; D014451:Ubiquinone / Q000096:biosynthesis*
D004286:Dolichols; D007527:Isoenzymes; D011106:Polyisoprenyl Phosphates; D014451:Ubiquinone; C015234:geranyl pyrophosphate; D002784:Cholesterol; D008148:Lovastatin; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D004122:Dimethylallyltranstransferase; D051231:Farnesyltranstransferase; D008798:Mevalonic Acid