Comparative studies of the responses of rat liver microsomal glucose-6-phosphatase and inorganic pyrophosphate-glucose phosphotransferase to phospholipase C treatment and phospholipid supplementation

A Reassessment of the Phospholipid Dependence of Membrane-Bound Enzymes, with Special Reference to GIucose-6-Phosphatase and Na+, K+-Dependent Adenosine Triphosphatase

“…Similarly, lysolecithin can either activate or inactivate the enzyme in untreated microsomes [11,20,70], but in this case the contrary effects may be elicited by the same concentration of lysolecithin, depending on the condi tions of the treatment. For example, a given concentration of lysolecithin may cause inactivation if incubated with microsomes at 37 °C, but may cause activation if the incubation is carried out at 5 or 20 °C, or at 37 °C in the presence of glucose-6-phosphate [11].…”

“…72], and the soluble phosphoryl derivatives, e.g., phosphorylcholine. The soluble products do not appear to affect glucose-6-phosphatase [7,20,70]. However, it has been shown con clusively that diglycerides produced by phospholipase C action can be further degraded to yield fatty acids by an acylhydrolase present in rat liver microsomes ; this release of fatty acids occurs even during phospholipase treatment at 5 °C and is markedly enhanced when phospholipase C-treated microsomes are subsequently incubated at 37 °C [10].…”

“…Phospholipase C. While phospholipase C hydrolyses all the phospholipid classes present in rat liver microsomes, phosphatidylcholine is attacked pre-ferentially [70]. The major products of the reaction are diglycerides, which remain associated with the membrane [20, cf.…”

“…The full activity of the enzyme may be unmasked by mild phospholipase or detergent treatment [26,33,86] or even by adding certain phospholipids before lipid depletion [70], (On the other hand, the addition of phospholipid before lipid depletion can cause inhibi tion [92]). The activation phenomenon and many of the problems already outlined are amply illustrated in the detailed examples which follow.…”

Liver Microsomal Glucose-6-phosphatase Is Competitively Inhibited by the Lipid Products of Phosphatidylinositol 3-Kinase

“…In the present work, we have addressed the question of the possible modulation of Glc6Pase activity by phospholipids themselves. Numerous previous studies have been devoted to the role of phospholipids in the stability and/or the activity of Glc6Pase by means of the effects induced by various phospholipases (11)(12)(13)(14)(15) or by phospholipid transfer proteins (15,16). None has specifically addressed the question of the effect of the phosphorylation of the inositol ring of phosphatidylinositol.Wehavepaidspecialattentionto3-phosphoinositides, the lipid products of phosphatidylinositol 3-kinase (PI3K) activity, since there is growing evidence to suggest that this enzyme is essential for insulin's regulation of glucose metabolism (see Ref.…”