V. BIOGENESIS AND METABOLISM 285 



no change in symptoms. Total fatty acids in the rats were highest in the 

 animals given linolenate plus pyridoxine, and these animals also contained 

 the greatest amounts of hexaenoic acid. The animals receiving linoleate 

 plus pyridoxine synthesized the largest amounts of arachidonic acid. These 

 results again point to the dual nature of the polyunsaturated acids: Lino- 

 leate is converted hy the animal 'principally to arachidonic acid and symptoms 

 of deficiency disappear, whereas linolenate is converted principally to hex- 

 aenoate and symptoms are not alleviated but growth and fat synthesis are 

 stimulated. Pyridoxine is involved in the conversion process, possibly as a 

 coenzyme in some enzyme system. 



Hove and Harris-'^ demonstrated a relationship between tocopherol and 

 linoleate. Tocopherol increased the effectiveness of suboptimal doses of 

 linoleate in preventing or curing essential fatty acid deficiency. The effect 

 was not limited to antioxidant action of the tocopherol within the gastro- 

 intestinal tract, for the effect was observed when the linoleate and tocoph- 

 erol were fed separately on alternate days. However, tocopherol fed alone 

 aggravates fat-deficiency symptoms. 



Anisfeld et alr^ were unable to show any relationship between linoleate 

 and tocopherol requirements in fat-deficient rats, using growth response 

 as a criterion. The metabolic relationship between tocopherol and essential 

 fatty acids is not clear, but suggestions have been made that tocopherol has 

 a sparing effect on the unsaturated acids by virtue of its antioxidant prop- 

 erties. 



The Conferences on Biological Antioxidants-^ produced much discussion 

 of possible in vivo antioxidant action. Tocopherol is a well-known effective 

 antioxidant in vitro, and suggestion has been made that it may act as an 

 antioxidant in living organisms. Little information has been brought to 

 bear on the problem. The keeping time of rat fats is extended by inclusion 

 of tocopherol in the diet.^^ Tocopherol has been shown to stimulate the 

 utilization of linolenate and oleate synthesis in rats,^^ and other antioxidants 

 have been shown to have a similar action. Dam and coworkers'** observed 

 that tocopherol-deficient rats deposit an oxidized polymerized fatty ma- 

 terial when fed highly unsaturated fats. This deposition of oxidized fat 

 contains peroxides and is presumably the result of abnormal oxidation of 

 the unsaturated acids. The effect is prevented by administration of cystine 



20 E. L. Hove and P. L. Harris. /. Nutrition 31, 699 (1946). 



21 L. Anisfeld, S. M. Greenberg, and H. J. Deuel, Jr., /. Nutrition 45, 599 (1951). 



22 IstSth Conferences on Biol. Antioxidants Josiah Macy, Jr. Foundation, New York 



(1946-1950). 



23 W. O. Lundberg, R. H. Barnes, M. Clausen, N. Larson, and G. O. Burr, J. Biol. 

 Chem. 168,379 (1947). 



2< H. Dam and H. Granados, Acta Physiol. Scand. 10, 162 (1945). 



