Inositol phospholipid and phosphatidic acid metabolism in response to membrane receptor activation

Abstract

The status of myo-inositol ( Fig. r(a)) as a vitamin is uncertain since some human tissues can synthesize it from glucose-6-phosphate. Eagle et a1. (1957), however, showed that it was an essential growth factor for many human cells in tissue culture. The concentration required for optimum growth was higher than would be expected of a typical vitamin, suggesting a metabolic role for inositol. It now seems clear that this role involves the phospholipids which contain inositol, phosphatidylinositol (PtdIns), phosphatidylinositol-4-phosphate (PtdInsqP; Fig. ~( b ) )and phosphatidylinositol-q,5-bisphosphate (PtdIns(,+,g)P,; Fig. ~( c ) ) . For the nutritionist these phosphoinositides are of interest in at least three ways. First, their metabolism is linked to activation of many cell-surface receptors, most of which mobilize calcium (Michell, 1975). Second, very recent studies connect the phosphoinositides with control of cell proliferation through epidermal growth factor and with malignant transformation of cells. Third, these lipids are rich in arachidonic acid and in some cells this particular pool of the acid is used as a source of prostanoids. The present paper concentrates on the first two of these topics since they are attracting a good deal of attention and some controversy. Phosphoinositides and

Phosphatidylinositol 4,5‐bisphosphate: Targeted production and signaling

“…At that time, PI4,5P 2 was thought to only serve as an intermediate in the PI cycle . Early studies identified a role for PI4,5P 2 as a precursor of other signaling molecules, such as inositol trisphosphate (IP 3 ) and diacylglycerol (DAG) . In the 1980s, the role of PI4,5P 2 as a precursor was further expanded via the discovery that PI4,5P 2 could be used as substrate for PI3K to produce phosphatidylinositol 3,4,5‐trisphosphate (PI3,4,5P 3 ) .…”

Resolution of the phosphoinositide-specific phospholipase C isolated from porcine lymphocytes into multiple species. Partial purification of two isoenzymes

“…Stimulation of many tissues with a number of agonists has been shown to result in a rapid turnover of phosphoinositides (Michell, 1975;Michell et al, 1981;Berridge, 1984;Hawthorne, 1985). This enhanced metabolism occurs not only in response to hormone stimulation, but also in cell lines stimulated with growth factors such as platelet derived growth factor (Berridge et al, 1984;Hasegawa-Sasaki, 1985), in T-lymphocytes stimulated with mitogenic lectins (Fisher & Mueller, 1968;Hui & Harmony, 1980;Hasegawa-Sasaki & Sasaki, 1983;Taylor et al, 1984) and in B-lymphocytes stimulated with anti-Ig antibodies (Maino et al, 1975;Guy et al, 1985;Coggeshall & Cambier, 1984;Bijsterbosch et al, 1985).…”