Phospholipids breakdown

The phospholipid breakdown product of this reaction, lysoleeithin, acts as a detergent and dissolves the membranes of red blood cells, causing them to rupture. Indian cobras kill several thousand people each year. 

Cassel GE, Koch M, Tiger G. 1995. The effects of cyanide on the extracellular levels of dopamine, 3,4,-dihydroxyphenylacetic acid, homovanillic acid, 5-hydroxyindoleacetic acid and inositaol phospholipid breakdown in the brain. Neurotoxicology 16(l) 73-82. 

Klein J, Chatterjee SS, Loffelholz K. (1997). Phospholipid breakdown and choline release under hypoxic conditions inhibition by bilobalide, a constituent of Ginkgo biloba. Brain Res. 755(2) 347-50. 

The drug is also a highly lipophilic base and accumulates in a number of tissues including the lung. This combination of extreme physicochemical properties can result in more specific interactions such as the condition of phospholipidosis (increase in total lung phospholipids) caused by inhibition of phospholipid breakdown [4]. The medicinal chemist has to decide if extreme lipophilicity and the presence of iodine are essential for activity and, in the case of amiodarone, proven clinical efficacy or whether alternative structures are possible. 

Taken together, these results showed that EGb can prevent ischemia-induced Na,K-AIPase injury, and suppress hypoxia- and ECS-induced membrane phospholipid breakdown in the brain, and bilobalide might be associated with its protective action. In addition, EGb reduces AA-induced neuronal damage as a consequence of the increase in reincorporation of AA Therefore, these mechanisms might provide a possible explanation for neuroprotective properties of EGb and bilobalide against oxidative damage. 

T6. The Action of Phospholipases The venom of the Eastern diamondback rattler and the Indian cobra contains phospholipase A2, which catalyzes the hydrolysis of fatty acids at the C-2 position of glycerophospholipids. The phospholipid breakdown product of this reaction is lysolecithin (lecithin is phosphatidylcholine). At high concentrations, this and other lysophospholipids act as detergents, dissolving the membranes of erythrocytes and lysing the cells. Extensive hemolysis may be life-threatening. 

Exton J.H., Taylor S.J., Augert G., and Bocckino S.B. 1991 Cell signalling through phospholipid breakdown. Mol Cell Biochem 104, 81-86. 

Simmonds SH, Strange PG (1985) Inhibition of inositol phospholipid breakdown by D2 dopamine receptors in dissociated bovine anterior pituitary cells. Neurosci Lett 60 267-272. 

Murayama T, and Ui M. (1987). Ihosphatidic add may stimulate menibrane receptors mediating adenylate cyclase inhibition and phospholipid breakdown in 3T3 fibroblasts. J. Biol. Chem. 262, 5522-5529. 

Several changes in ion membrane homeostasis also occur from fatty acid and long chain acylcamitines (LCAC) accumulation or from the formation of lysophosphadyl-choline (LPC) and arachidonic acid (AA) due to phospholipid breakdown by lipases. In fact, fatty acids and AA favor activation of K+ outward current while LCAC and LPC favor inward over outward current, reviewed by Carmeliet.55... 

Ross BM, Hudson C, Erlich J, Warsh JJ, Kish SJ. Increased phospholipid breakdown in schizophrenia— evidence for the involvement of a calcium-independent phospholipase A(2). Arch Gen Psychiatry 1997 54 487 94. 

Little is known of the intracellular events involved in the augmentation of cyclic AMP accumulation elicited by H, -receptors in mammalian brain slices. However, it seems certain that another second messenger is involved, since the effect is not observed in membrane preparations [81, 205]. Calcium appears to be important for the response, since removal of external calcium reduces H,-receptor-mediated cyclic AMP accumulation in guinea-pig cerebral cortical slices [206]. Inositol phospholipid breakdown or its products (inositol trisphosphate and diacylglycerol) may also be involved, since H,-receptor stimulation is accompanied by an accumulation of inositol phosphates in slices of guinea-pig cerebral cortex [60, 207, 208]. Inositol trisphosphate may then... 

Initial studies in rat brain showed that intracistemal injection of histamine stimulated the incorporation of [33P]P into inositol phospholipids [235, 236]. Studies with selective H,- and H2-agonists and antagonists further suggested that this response was mediated by H,-receptors [236]. Increased turnover of inositol phospholipids is nevertheless a rather indirect measure of the initial receptor-mediated event, namely breakdown of phosphatidylinositol 4,5-bisphosphate. A more direct and sensitive method of monitoring inositol phospholipid breakdown is now available, however, following the discovery that Li+ ions can cause an accumulation of inositol 1-phosphate in slices of rat cerebral cortex and parotid gland as a result of inhibition of inositol 1-phosphatase [237],... 

Early studies of histamine-induced inositol phospholipid breakdown in guinea-pig brain slices detected large accumulations of inositol 1-phosphate but very little change in the levels of the more polar inositol phosphates, inositol... 

Schafer, A.I., Maas, A.K., Ware, A., Johnson, P.C., Rittenhouse, S. and Salzman, E.W. (1986). Platelet protein phosphorylation, elevation of cytosolic calcium, and inositol phospholipid breakdown in platelet activation induced by plasmin. ]. Clin. Invest., 78, 73-79... 

Nakamura T, Ui M (1985) Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release and histamine secretion in mast cells by islet-activating protein, pertussis toxin. A possible involvement of the toxin-specific substrate in the Ca -mobilizing receptor-mediated biosignaling system. J Biol Chem 260 3584-3593... 

P. is - prostaglandin that is produced by enzymatic transformation of prostaglandin endoperoxides and which dilates blood vessels. P. is chemically unstable in aqueous solutions, but the mono sodium-salt is stable as a solid and in solution. In addition, p. shows antimetastatic effects and has been used for patients with acute myocardial infarction. It has also been postulated that p. acts to stimulate platelet adenylate cyclase and to prevent the action of thrombi in phospholipid breakdown as well as platelet aggregation. In clinical practice, it is used for preventing the loss of platelets in cases wdiere the blood comes into extracorporal contact with artificial surfaces, i.e., in hemodialysis, cardiopulmonary bypass, and charcoal column perfusion for treatment of liver failure. 

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