The De Novo Phospholipid Synthesis Effect: Occurrence, Characteristics, Underlying Mechanisms and Functional Significance in Hormone Action and Secretion

Summary

A number of hormones and other agents have been found to provoke rapid, relatively large increases in phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP₂) and diacylglycerol (DG) in certain of their target tissues. This effect is due to de novo synthesis of PA and may be the consequence of increased availability of substrate (e.g., glycerol 3-P) or increased activity of glycerol 3-P acyltransferase. This “de novo effect” appears to be a post-second messenger event and, in some tissues, may be the consequence of increases in cAMP and/or Ca²⁺. Increases in PA, DG, PIP and PIP₂ (and possibly inositol-phosphates) may serve to alter the uptake and distribution of cellular Ca²⁺ and increase protein kinase C activity. Changes in local concentrations of lipids and phospholipids may also provoke direct effects on membrane-bound receptors, transporters and enzymes. The de novo phospholipid effect may be important in the following: (a) regulation of steroidogeness by ACTH, luteinizing hormone, angiotensin and K in adrenal and ovarian tissues; (b) insulin action on pyruvate dehydrogenase and glucose and lipid metabolism in adipose tissue and muscle; (c) handling of Farese Ca²⁺ and PO₄ ³⁻ in parathyroid hormone-sensitive tissues; (d) light-stimulation of the retina; and (e) glucose-induced insulin secretion in pancreatic islets.