Harold W. Moore

Vitamin E deficiency in the monkey: VII. The role of vitamin E and the vitamin-like activity of coenzyme Q☆

Abstract Young Rhesus monkeys were fed a vitamin E-deficient purified diet containing, by weight, 11% fat and 18% isolated soybean protein. After 1–2 years they developed the characteristic deficiency syndrome of nutritional muscular dystrophy and anemia. The syndrome was not influenced by extra dietary methionine and cystine, by the presence or absence of choline, or by selenium. Complete remission of the muscular dystrophy and anemia was induced either by d -alpha-tocopherol or by its l -epimer, but the duration of the remission after treatment with the l -epimer was relatively short. Coenzyme Q 10 treatment evoked a reticulocytosis in the anemic, vitamin E-deficient monkey, and a complete hematologic remission followed treatment with a compound of lower molecular weight, hexahydrocoenzyme Q 4 . This response was interpreted to mean that vitamin E either is involved in the maintenance of coenzyme Q activity or can substitute for coenzyme Q.

Studies on the mechanism of vitamin-like activity of coenzyme Q

Abstract A vitamin E-deficient diet has been used to produce dystrophy in rabbits. This diet may be considered as an antioxidant-deficient diet because of the lack of structural specificity for vitamin E. Importance is attached to the previous recognition of widespread metabolic damage by such a diet, due to lipid peroxidation, including mitochondrial lipids. Coenzyme Q and its precursors, beginning with 3-decaprenyl-4-hydroxybenzoic acid, are all polyunsaturated lipids and presumably components of mitochondrial membranes. Clearly, coenzyme Q and its precursors are exposed to peroxidation on an antioxidant-deficient diet. Consequently, there may be inadequate levels of coenzyme Q in an animal living on a diet favorable to such peroxidation of lipids. Data supporting low tissue levels of coenzyme Q are yet inconclusive. Hexahydrocoenzyme Q 4 has shown life-saving and vitamin-like activity in the dystrophic rabbit by three criteria: (a) normalization of crcatine-creatinine ratio; (b) regaining of righting reflex; and (c) weight gain. There was no detectable conversion of radioactive 6-chromanol of hexahydrocoenzyme Q 4 to radioactive hexahydrocoenzyme Q 4 or coenzyme Q 10 . Since hexahydrocoenzyme Q 4 , like coenzyme Q 10 , is active for electron transfer in the succinoxidase system, it is evident that the response to hexahydrocoenzyme Q 4 by the rabbit can be due to restored levels of CoQ in the tissue. CoQ 4 substitutes for CoQ 10 and restores the functioning of electron transfer in respiration and coupled oxidative phosphorylation. Since neither the 6-chromanol of hexahydrocoenzyme Q 4 nor α-tocopherol is active for electron transfer in the succinoxidase system, and since there is no apparent conversion of the CoQ-chromanol to the quinone, it is evident that these two chromanols appear to function solely as structurally nonspecific antioxidants which can protect not only tissue levels of CoQ 10 and its precursors but also other body unsaturated lipids against diminution by peroxidation. By such protection, required tissue levels of CoQ 10 could be maintained through intrinsic biosynthesis.

Synthesis of 2,5-H-2,5-azepindiones from quinones and hydrazoic acid☆

Abstract 2,5-H-2,5-Azepindiones have been prepared by the reaction of substituted quinones with hydrazoic acid in a significantly clarified manner. Such 7-membered ring compounds are now readily available in high yields. The reaction conditions are important to obtain these and not other products. 2,5-H-2,3,6-Trimethyl-2,5-azepindione, 2,5-H-3-methyl-6-isopropyl-2,5-azepindione, 2,5-H-6-methyl-3,4-benzoazepin-2,5-dione, 2,5-H-3,6-dimethyl-2,5-azepindione and 2,5-H-3,4,6,7-tetramethyl-2,5-azepindione have been synthesized. The NMR spectra of the azepindiones and their bromo derivatives are essential data to substantiate structural assignments. The reaction takes place on the least hindered carbonyl group and the inserted NH group is attached to the least substituted carbon atom.

COENZYME Q. LX. VITAMIN-LIKE ACTIVITY OF COENZYME Q.

Summary Vitamin-like activity for hexahydrocoenzyme Q4 in the dystrophic rabbit is demonstrated. This activity for a quinone member of the CoQ group is comparable to the activity of α-tocopherol and CoQ4-chromanol which has previously been demonstrated. By contrast, a sample of 2,3,5-trimethyl-6-phytylbenzoquinone, which was free of contamination with α-tocopherol, exhibited only a low order of activity in the dystrophic rabbit. The dystrophic rabbit failed to recover when coenzyme Q10 was administered orally; it is apparent that the administered CoQ10 failed to reach its mitochondrial and microsomal sites since a lower homolog, hexahydrocoenzyme Q4, exhibits activity in the dystrophic rabbit. It is considered that CoQ10, which is normally present in rabbit tissue, does inherently have this vitamin-like activity.