624 Bioehimica et Biopt~vsica A cta 856 (1986) 624-628 Elsevier BBA 73054 The effect of gluconeogenesis on phospholipid turnover in isolated chick proximal tubule cells Riffat Parveen, Michael F. Grahn and Peter J. Butterworth Department of Biochemistry, King's College (Kensington Campm), Campden Hill Road, London W8 7AH (U.K.) (Received October 8th, 1985) Key words: Gluconeogenesis; Phospholipid turnover; Phosphate transport; (Chicken kidney) Previous work from this laboratory has shown that isolated chick renal proximal tubule cells possess an Na+-dependent Pi transport system and that Pi uptake is stimulated under gluconeogenic conditions. It is shown in the present paper that gluconeogenesis is associated with a rapid incorporation of Pi into membrane phospholipids, particularly phosphatidylinositol, and some evidence has been obtained for a change in the relative amounts of phosphatidylinositol polyphosphates under gluconeogenic conditions. There is no increase in the total phospholipid phosphate content however, suggesting that pyruvate-induced incorporation of Pi into phospholipids represents accelerated turnover rather than a net increase in synthesis. It is suggested that the stimulation of Na+-dependent Pi uptake by pyruvate is related to the increased rate of phospholipid turnover. Thus Pi transport may be a further example of a physiological system that is influenced by phosphatidylinositoi metabolism. The role of phosphatidylinositol phosphates could be to stimulate transfer of transporter molecules from internal stores to the brush-border membrane of the cell. Introduction Isolated proximal tubule cells from chick kid- ney take up Pi in a sodium-dependent process that is sensitive to inhibition by parathyroid hormone [1] and to stimulation by phosphate depletion [2]. In addition the cells are metabolically competent and actively produce glucose from pyruvate by gluconeogenesis [3]. As such they are suitable for studying biochemical events in the regulation of phosphate reabsorption by the kidney by various humoral agents. The isolated cells from chick kidney take up Pi Abbreviations: P,, inorganic phosphate; PI, phosphati- dylinositol; PC, phosphatidylcholine; PE, phosphatidy- lethanolamine; PS, phosphatidylserine; PA, phosphatidic acid; PIP, phosphatidylinositol 4-phosphate; PIP2, phosphati- dylinositol 4,5-bisphosphate. at a greater rate in the presence of a gluconeogenic substrate such as pyruvate than when supported on glucose as the respiratory substrate. Also when gluconeogenesis is blocked by the metabolic in- hibitor 3-mercaptopicolinate [3], the stimulation of Pi uptake is also abolished [4]. The pyruvate-in- duced stimulation in P~ uptake occurs within two minutes, does not seem to originate from an elevated cellular ATP level, but may reflect in part a change in the intracellular organic phosphate/P~ ratio. The rapidity of the pyruvate effect suggests that a mechanism other than de novo synthesis of transporter molecules is responsible for the in- crease in Na+-dependent P~ transport capacity. There is growing interest in the role of phos- phatidylinositol metabolism in the expression of the physiological effects of many hormones and neurotransmitters [5]. Parathyroid hormone has been demonstrated to increase the levels of phos- 0005-2736/86/$03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)