TOCOPHEROLS IN VARIOUS METABOLIC PROCESSES 707 



had been on diets free from vitamin E, or containing \itamin E, respec- 

 tively, for the preceding five months. The incorporation of radiocarbon 

 into the ribonucleic acid and desoxyribonucleic acid fractions was con- 

 siderably' greater in the tissues of the vitamin E-deprived rats than it was 

 in the controls. ^^^ When 1 mg. of a-toeopheryl phosphate was admin- 

 istered to the ^•itamin E-deficient rats one hour before the C^^-formate 

 was given, the rate of incorporation of labeled carbon into the nucleic acids 

 was significantly reduced. It was also found ^"* that vitamin E deficiency, 

 in the rabbit resulted in a marked increase in the incorporation of radio- 

 active phosphorus (P^-) into tissue nucleic acids. Even greater differences 

 in the nucleic acid synthesis of skeletal muscle and bone marrow character- 

 ized vitamin E-deficient and vitamin E-fed rabbits.^- It is believed by 

 Dinning^^® and by Diiniing et al^^""^ that a-tocopherol regulates the syn- 

 thesis and degradation of nucleic acid as one of its primary functions. 



b. Carbohydrate Metabolism, (a) Pyruvic Acid Formation. Bellotti 

 and Mezzano^-^^ called attention to the fact that the concentration of 

 pyruvic acid is decreased in the blood and liver of vitamin E-deficient rats. 

 Since this intermediate substance is so intimately bound up with carbo- 

 hydrate metabolism, it is e\'ident that tocopherol must play a role in nor- 

 mal carbohj'-drate breakdoA\m. Howe^'er, it is not kno^Mi which of the 

 metabolic pathways is regulated by tocopherol. 



(b) Action on Cytochrome c Reductase. Houchin^^^ was the first to 

 postulate that tocopherol functions as an inhibitor of cytochrome c reduc- 

 tion in the metabolism of skeletal muscle. This hj'pothesis was based 

 upon the increased rate of succinic acid oxidation in dystrophic muscle 

 of the hamster, '^^ and the depressing effect upon oxygen consumption.'*" 

 Howe\'er, the succinic dehydrogenase system is apparently not directly 

 invoh'ed in nutritional muscular dystrophy.'^' More recently, on the 

 basis of additional data, Nason and Lehman'^- have come to the conclusion 

 that the tocopherols specifically stimulate cj^tochrome c reductase. The 

 stimulating effect was noted in the case of the particulate matter from 

 several sources following extraction with isooctane, but the tocopherol was 

 ineffective in augmenting the action of pure cytochrome c reductase. It is 

 therefore believed that there may be a lipid co-factor in the crude c\^to- 

 chrome c reductase which is specifically related to the tocopherols. 



»"« J. S. Dinning, J. T. Sime, and P. L. Day, /. Biol. Chem., 222, 215-217 (1956). 

 1=8 R. Bellotti and M. Mezzano, Inform, med. Sez. din. sci., 6, 238-241 (1952); Chem. 

 Abst., 47, 3944 (1953). 



159 O. B. Houchin, /. Biol. Chem., 146, 313-321 (1942). 



i«> O. B. Houchin and H. H. Mattill, /. Biol. Chem., 146, 301-307, 309-312 (1942). 



'" D. H. Basinski and J. P. Hummel, /. Biol. Chem., 167, 339-343 (1947). 



"» A. Nason and I. R. Lehman, Science, 122, 19-22 (1955). 



