Nutritional Regulation of the Composition, Metabolism, and Function of Cellular Phosphatidylinositol

Summary

Molecular species analyses have revealed that in most mammalian cells the 1-stearoyl 2-arachidonoyl species of phosphatidylinositol predominates greatly over other species and this may be significant in the functioning of this phospholipid. Tracer studies conducted in vivo and enzyme studies have suggested the importance of deacylation-reacylation reactions for the formation of the 1-stearoyl 2-arachidonoyl species and the enrichment of phosphatidylinositol with arachidonic acid via acylCoA: acyl-sn-glycero-(3)phosphoinositol acyltransferase activity. Our laboratory has also been interested in the influence of nutritional status on the physiological levels of myo-inositol and phosphatidylinositol in health and disease and on the fatty acid composition of phosphatidylinositol since such dietary-induced alterations could modify its cellular functioning. Inositol-deficient diets have been shown to produce a reduction in phosphatidylinositol levels and a marked accumulation of hepatic triglyceride in several animal species. The consumption of certain types of dietary fatty acids (e.g., fish oils containing eicosapentaenoic acid) produces a lowering of the arachidonoyl phosphatidylinositol in human platelets and provides for the introduction of novel molecular species (eicosapentaenoyl phosphatidylinositol) which may be related to the accompanying reduced platelet aggregation.

Dietary cholesterol supplementation was found to cause an elevation in the concentration of total and arachidonoyl phosphatidylinositol in the platelets of gerbils. Human subjects with hypercholesterolemia also have elevated levels of phosphatidylinositol and cholesterol (expressed as µg/10⁸ platelets) which may be associated with the increased platelet aggregability. Patients with chronic renal failure exhibit a dramatic hyperinositolemia without a marked alteration in the circulating levels of lipoprotein-bound phosphatidylinositol although its fatty acid composition is abnormal. These results indicate that the concentration of cellular phosphatidylinositol and the relative amounts of the various molecular species, including the arachidonoyl species, are subject to significant nutritional modification which may offer clinical applications in the control of phosphatidylinositol-mediated physiological responses.