The effect of vitamin A on ubiquinone and ubichromenol in the rat, and its relation to the effect of vitamin E.

Ubiquinone was first observed in the organs of vitamin A-deficient rats (Festenstein, Heaton, Lowe & Morton, 1955)~ and Morton and his co-workers have shown that vitamin A deficiency leads to the accumulation of both ubiquinone and its cyclic isomer, ubichromenol, in the liver of the rat (see, for example, Heaton, Lowe & Morton, 1957; Morton & Phillips, 1959). In an attempt to ascertain whether an increase in ubiquinone is an essential part of the deficiency syndrome, Lowe, Morton, Cunningham & Vernon (1957) examined the livers of vitamin A-deficient fowls and found no such increase in this species. Moore & Sharman (1960), although they agreed that liver ubiquinone concentration is increased during vitamin A deficiency in the rat, suggested that a good deal of the increase is caused by the severe diminution in weight of the liver, and they were unable to find a corresponding increase in the heart. They concluded, on rather limited evidence, that the effect might be limited to liver. Gloor & Wiss (1959a), on the other hand, found that the uptake of mevalonic acid into ubiquinone was increased in vitamin A-deficient rat liver and suggested that vitamin A is concerned at the metabolic level with isoprenoid synthesis. Edwin, Diplock, Bunyan & Green (1961) have shown that the synthesis of ubiquinone and ubichromenol in the rat is markedly influenced by vitamin E, and Green, Diplock, Bunyan & Edwin (1961) have drawn similar conclusions from a study of the rabbit. I t was already observed in both these investigations that the concentration of vitamin A in the tissues was not apparently related to the ubiquinone concentration and, in a preliminary communication, Green, Edwin, Diplock & Bunyan (1960) have suggested that much of the effect of vitamin A on ubiquinone concentrations could be explained by simultaneous variations in tocopherol concentrations. The relationship between vitamins E and A is, in fact, so intimate that it is essential to investigate in considerable detail their influence on each other and on ubiquinone. The effect of vitamin A-uncomplicated by vitamin E-is not easy to study. When the amount of vitamin A in the diet of the rat is increased, the result is nearly always to diminish the concentrations of tocopherol in the tissues, which, as Edwin et al. (1961) have demonstrated, nearly always leads to a decrease in ubiquinone. The effect of vitamin E on ubiquinone-free of vitamin A effects-is easier to investigate, since vitamin E in the diet usually increases vitamin A in the tissues; thus, any effect of vitamin E in increasing the ubiquinone concentration must be unrelated to vitamin A, whose postulated effect would be in the reverse direction. Here we describe experi-