Effects of selenium supplement on the de novo biosynthesis of glycerolipids in the isolated rat heart

The effect of selenium supplement on glycerolipid biosynthesis in the isolated rat heart was investigated. Selenium was administered to the rat by intraperitoneal injection of 4.33 μmol/kg per day for 3 consecutive days. Animals administered with an equal volume of saline were used as controls. Hearts from both animal groups were perfused in Krebs-Henseleit buffer containing labelled glycerol. Subsequent to perfusion, the radioactivity associated with each glycerolipid group was determined. Selenium supplement caused elevations in the labelling of phosphatidic acid and phosphatidylcholine but not in other phospholipids, diacylglycerol or triacylglycerol. The mechanisms for the enhancement of labelling into phosphatidic acid and phosphatidylcholine were examined. The activity of the enzymes responsible for the synthesis of phosphatidic acid in the rat heart was not changed by selenium supplement. However, a 51% increase in the acyl-CoA level was detected which might account for the elevated labelling of phosphatidic acid in the selenium supplemented animal. The 2-fold increase in the activity of CDPcholine:diacylglycerol cholinephosphotransferase might also account for the increase in the labelling of phosphatidylcholine in the heart of the selenium-supplemented rat. It is clear from this study that selenium plays a regulatory role in the control of cellular lipid metabolism.link_to_subscribed_fulltex

The modulation of phosphatidylinositol biosynthesis in hamster hearts by methyl lidociane

Methyl lidocaine is an experimental anti-arrhythmic drug which has been shown to enhance the biosynthesis of phosphatidylinositol (PI) in the hamster heart, In this study, the effect of methyl lidocaine on enzymes involved in the biosynthesis of PI in the heart was examined. When the hamster heart was perfused with labelled methyl lidocaine, the majority of the compound was not metabolized after perfusion. The direct action of methyl lidocaine on an enzyme was studied by the presence of the drug in enzyme assays, whereas its indirect action was studied by assaying the enzyme activity in the heart after methyl lidocaine perfusion. CTP:phosphatidic acid cytidylyl-transferase, a rate-limiting enzyme in PI biosynthesis, was stimulated by methyl lidocaine in a direct manner. Kinetic studies revealed that methyl lidocaine caused a change in the affinity between the enzyme and phosphatidic acid and resulted in the enhancement of the reaction. Alternatively, acyl-CoA: lysophosphatidic acid acyltransferase, another key enzyme for PI biosynthesis, was not activated by the presence of methyl lidocaine. However, the enzyme activity was stimulated in hearts perfused with methyl lidocaine. The enhancement of the acyltransferase by methyl lidocaine perfusion was found to be mediated via the adenylate cyclase cascade with the elevation of the cyclic AMP level. The stimulation of protein kinase A activity by cyclic AMP resulted in the phosphorylation and activation of the acyltransferase, Interestingly, the activity of protein kinase C was not stimulated by methyl lidocaine perfusion. We conclude that the enhancement of PI biosynthesis by methyl lidocaine in the hamster heart resulted from the direct activation of the cytidylyltransferase, as well as the phosphorylation and subsequent activation of the acyltransferase.link_to_subscribed_fulltex

The effect of methyl lidocaine on lysophospholipid metabolism in hamster heart

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Combination of the anti-tumour cell ether lipid edelfosine with sterols abolishes haemolytic side effects of the drug

Edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) is an anti-tumour cell ether lipid with surface-active properties. Pure edelfosine can be dispersed in aqueous media in the form of micelles. One important, negative side effect of edelfosine is that it is highly haemolytic. In this paper, we show that edelfosine can be co-dispersed in water with certain lipids (particularly cholesterol, campesterol or β-sitosterol) so that it gives rise to liposomes. Surface pressure measurements demonstrate that edelfosine is slowly released from these liposomes. In liposomal form, edelfosine remains apoptogenic for a variety of leukemia cell lines, while its haemolytic effect is abolished. The phenomenon is explained on the basis of the complementarity of the molecular geometries of sterols and edelfosine