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Effect of Degree of Fatty Acid Unsaturation in Tocopherol Deficiency-induced Creatinuria¹

L. B. Mendel Research Laboratory, Elgin State Hospital, Elgin, Illinois, and Department of Biological Chemistry, University of Illinois College of Medicine, Chicago, Illinois

The rate of development of creatinuria, in the tocopherol-deficient rat proved to be dependent on the degree of unsaturation of the dietary fatty acids. Data were obtained consistent with relative in vivo rates of fatty acid peroxidation of monoenoic, dienoic, trienoic, tetraenoic, pentaenoic, and hexaenoic fatty acids in the ratios 0.025:1:2:4:6:8, and tocopherol requirements for constant diminution in the rates of peroxidation in the ratios 0.3:2:3:4:5:6. Muscle phospholipid fatty acid compositions were dependent on the compositions of the dietary fats but were independent of the level of dietary fat between 7.5 and 19%. Within this range the rates of development of creatinuria and the tocopherol requirements were also independent of the level of dietary fat. One milligram of d-a-tocopheryl acetate per kilogram rat per week delayed the onset of creatinuria by 17 to 20 weeks. When the diet contained suboptimal levels of selenium and sulfur amino acids, creatinuria occurred 30% more rapidly and the tocopherol requirement increased tenfold. Lower levels of the most highly unsaturated fatty acids were noted in the muscle phospholipids of the tocopherol-deficient animals. This is consistent with the concept that susceptibility toward peroxidation increases as the number of double bonds per fatty acid increases.

Manuscript received 8 August 1963.