TOCOPHEROLS IX VARIOUS METABOLIC PROCESSES 731 



the sulfur-eontaining amino acids, ^""~^^- or on diets eontaining certain 

 yeasts^^®'^*^'^^^ which are lacking in "Factor 3" as, for example, American 

 torula yeast. ^^^ In the absence of these several components, a sudden 

 massive necrosis occurs in the liver of the rat, together with hemor- 

 rhage, ^^^••■'"•^^'~''^'' or with lung hemorrhages^^" which are the cause of 

 death. Schwarz, Chernick, et al^^*~^^^ described the necrotic liver de- 

 geiieration which occurs several weeks after a metabolic lesion charac- 

 terized by a rapid decline in oxygen consumption by liver slices after a 

 thirty-minute period of normal respiration. This metabolic upset is be- 

 lie\''ed to be due to an interference in oxidative phosphorylation in some 

 way related to the Krebs cycle. ^''^"^'"^ Both the preliminary metabolic 

 phase and the succeeding morphologic changes can be prevented by a- 

 tocopherol, while the metabolic changes can be countei-acted either l)y a- 

 tocopherol or by a-tocopherylhydroquinone. 



Hove'^" described a somewhat simpler form of liver injury, which occurs 

 in rats on low-protein diets deficient in the sulfur-containing amino acids, 

 when hepatotoxic agents such as triorthocresyl phosphate, carbon tetra- 

 chloride, or pyridine are given; this condition can be alleviated by in- 

 creasing either the protein or the tocopherol intake. It is the opinion of 

 Hove"*' that the hepatotoxic agents function as prooxidants in unsaturated 

 lipid systems; this results in the formation of peroxides and in a reduction 

 of the tocopherol in the tissues. If this hj'-pothesis is correct, tocopherol 

 would act by alleviating the state of tissue peroxidation. Sellers et al.^^'' 

 suggest that tocopherol may protect — SH groups, so that they are avail- 

 able for detoxication reactions. Olson and co-workers-^'^^ postulate that 



5" P. Gyorgy and H. Goldblatt, /. Exptl. Med., 89, 245-268 (1949). 



368 K. Schwarz, Z. physiol. Chem., 281, 101-108 (1944); 283, 106-112 (1948). 



'59 K. Schwarz, Ann. New York Acad. Sci., 62, 225-230 (1949). 



3«»E. L. Hove, D. H. Copeland, and W. D. Salmon, /. Nutrition, 30, 397-467 (1949). 



3" M. Goettsch, J. Nutrition, 44, 443-454 (1951). 



3«2 O. Lindan and H. P. Himsworth, Brit. J. Exptl. Pathol., 31, 651-663 (1950). 



363 P. Gyorgv, C. S. Rose, R. M. Tomarelli, and H. Goldblatt, ./. Nutrition, 41, 265-278 

 (1950). 



3"K. Schwarz, S. S. Chernick, C. P. Rodnan, J. G. Moe, and W. Mertz, Dietary 

 Necrotic Liver Degeneration: Occurrence of a Specific Defect Reversible by Intraportal Vita- 

 min E, Abst. Reports Third Intern. Congr. on Vitamin E, Venice, 1955, Vol. I, p. 30. 



3«5 K. Schwarz, Ann. New York Acad. Sci., 57, 878-888 (1954). 



366 S. S. Chernick, C. P. Rodnan, and K. Schwarz, Federation Proc, 13, 191 (1954); 

 S. S. Chernick, J. G. Moe, and K. Schwarz, Ibid., 14, 191-192; G. P. Rodnan and K. 

 Schwarz, 270 (1955). 



367 E. A. Sellers, R. W. You, and C. C. Lucas, Proc. Soc. Exptl. Biol. Med., 75, 118-121 

 (1950). 



368 R. E. Olson, C. S. Yang, M. Riegl, and B. Stewart, Federation Proc, 14, 447 (1955). 



