Date of Award
Doctor of Philosophy
John T. Smith
Mary Rose Gram, Kenneth J. Monty, Frances A. Schofield
An interaction between inorganic sulfur and cod liver oil (CLO) has been proposed in the normal metabolism of the albino rat after a gross malformation of the hind limbs was observed in rats fed a diet low in sulfate and without CLO. The rats were fed these diets from the time they were two weeks of age through the seventh week of life. Toward the end of this period, the fourth week after weaning, the lesion was observed. The study included four basic variations of a diet low in sulfate: with and without CLO and with and without vitamin E. It was concluded that there was present in CLO a factor which enhanced normal production of the sulfated mucopolysaccharides. The present study was an attempt to identify the "active factor" in CLO.
Methods for extracting vitamin D sulfate, sulfolipids or modification of either procedure were followed in an attempt to fractionate CLO and isolate the "active factor." The extensive fractionation of CLO failed to concentrate the desired factor in any one fraction of CLO but rather indicated the factor to be associated with any lipid fraction. Rather than continue with an apparently fruitless fractionation of CLO, model systems were sought that would mimic the effect of CLO.
Thus, two sources other than CLO of long-chain polyunsaturated fatty acids were fed (safflower oil or 55 percent pure linolenic acid). The results of the first system confirmed the effect of long-chain polyunsaturated fatty acids to be similar to that of CLO when fed to rats. Since the synthesis of lecithin, especially in female rates, involves the utilization of S-adenosylmethionine, a lecithin deficiency could develop in those rats fed diets low in sulfate and without CLO. Thus, diets with added lecithin, choline and 0.1 percent of sulfate were fed to rats. Results of that study supported the theory that dietary long-chain polyunsaturated fatty acids such as those supplied by CLO accelerated the metabolism of lecithin.
The relationship between increased lecithin metabolism and increased endogenous sulfur was then investigated. When methionine-1-14C was given to rats fed 0.5 percent methionine and 5 percent CLO or no CLO, there was a statistically significant increase in the metabolism of the carbon skeleton of methionine by rats fed diets low in sulfate but supplemented with CLO. Since this result indicated that more methionine was metabolized to provide more S-adenosylmethionine for the methylation of posphatidylethanolamine, then presumably more homocysteine escaped from the remethylation cycle and was converted to cysteine and eventually to sulfate. consequently, the oxidation of methionine-35S to 35SO4= was measured using liver preparations taken from rats fed the above diets. The results of this experiment showed a statistically significant increase in oxidation of methionine-35S to 35SO4= by the liver homogenates from rats fed diets low in sulfate and supplemented with CLO. Therefore, it is concluded that rather than containing an "active factor" it is the long-chain polyunsaturated fatty acids in CLO which are responsible for its apparent effect on sulfur metabolism.
Morris, Jayne Tigert, "An Explanation for the Apparent Effect of Cod Liver Oil on Sulfur Metabolism in the Albino Rat. " PhD diss., University of Tennessee, 1971.