Date of Award
Doctor of Philosophy
John T. Smith
Sharon L. Melton, Betty R. Carruth, Betsy Haughton
The test hypothesis of this investigation was that methionine-supplemented diets could possibly interfere with the metabolism of polyunsaturated fatty acids, thereby altering the biosynthesis of the active metabolites, prostanoids, and the profiles of tissue phospholipids. The postulated mechanism of action for this dietary regimen would be to increase the tissue concentration of the active methyl donor, S-Adenosyl-methionine (SAM) which is also called an activated methionine. SAM is a potent inhibitor of the cycloaxygenase enzyme which is important for the synthesis of biologically active prostanoids.
The results demonstrated that liver microsomes from rats fed the methionine-supplemented diet had a statistically significant decrease in cyclaoxygenase activity. However, metabolic regulation of the polyunsaturated fatty acids metabolism is controlled by a host of enzymes and in a dynamic equilibrium state. Measurement of the incorporation of eicosapentaenoic and arachidonic acids into the phosphatidylinositol fraction of rat tissues demonstrated no difference among the rats fed the control, cysteine-supplemented, and methionine-supplemented diets.
The differential incorporation of polyunsaturated fatty acids into phosphatidylinositol fraction by various tissues was partially explained by the apparent Kms for both arachidonic and eicosapentaenoic acids of fatty acyl-CoA synthetase in liver and brain tissues. Many other factors and enzymes which regulate the metabolism of phospholipids and the mechanism of action of SAM need to be elucidated in the future research on the beneficial effect of a methionine-supplemented diet.
Therefore, one part of the null hypothesis is rejected and restated that supplemental methionine has an effect on the metabolism of polyunsaturated fatty acids through the cycloaxygenase enzyme pathway. The other part of the null hypothesis that supplemental methionine has no effect on the incorporation of polyunsaturated fatty acids into tissue phospholipids remains to be further investigated.
Chen, Mei Fung, "The Effect of Dietary Sulfur on the Metabolism of Long Chain Polyunsaturated Fatty Acids. " PhD diss., University of Tennessee, 1988.