Stimulation of coenzyme Q synthesis.
Uptake of dietary coenzyme Q (CoQ) into organs is limited but there are some exceptions such as adrenal glands and ovaries. Under deficient conditions an optimal solution could be stimulation of the endogenous synthesis. In rodent exercise, cold exposure and a few substances elevate the CoQ levels to some extent. Investigations of the nuclear receptors PPARalpha, RXRalpha and LXRalpha&beta did not answer the question which nuclear receptor regulates CoQ biosynthesis and at present we cannot design a ligand for upregulation of the synthesis. Upon ultraviolet irradiation of CoQ a number of products are formed which influence the synthesis of the mevalonate pathway lipids. Among them epoxidated derivatives were identified. Upon chemical epoxidation of a series of polyisoprenoids it was found that none of the tested poly-cis polyisoprenols had any effect but some of the all-trans polyisoprenols stimulated CoQ synthesis and in some cases also inhibited cholesterol biosynthesis. Tocotrienol epoxides were proved to be very efficient, those having one epoxide in the side chain doubled or trebled the CoQ synthesis while those with two epoxides additionally also inhibited cholesterol synthesis by 50-90%. The elevation of CoQ synthesis was elicited by increased mRNA levels for biosynthetic enzymes while the inhibition point in the cholesterol synthesis was localized to oxidosqualene cyclase.
Bentinger
Magnus
M
Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Tekle
Michael
M
Brismar
Kerstin
K
Chojnacki
Tadeusz
T
Swiezewska
Ewa
E
Dallner
Gustav
G
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000494:pharmacology; D003080:Cold Temperature; D004268:DNA-Binding Proteins / Q000502:physiology; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D057093:Orphan Nuclear Receptors; D010053:Ovary / Q000378:metabolism; D047493:PPAR alpha / Q000502:physiology; D005082:Physical Exertion / Q000502:physiology; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D047490:Retinoid X Receptor alpha / Q000502:physiology; D013729:Terpenes / Q000494:pharmacology; D014451:Ubiquinone / Q000096:biosynthesis* / Q000378:metabolism
D004268:DNA-Binding Proteins; D004852:Epoxy Compounds; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha; D018160:Receptors, Cytoplasmic and Nuclear; D047490:Retinoid X Receptor alpha; D013729:Terpenes; D014451:Ubiquinone; D002784:Cholesterol