Brain phosphatides

On hydrolysis of the phosphatides, myo-inositol monophosphate—and, from a brain phosphatide, a diphosphate—is obtained but, these products have, in most cases, not been adequately characterized, and it is not yet known whether all phospholipids contain the same myo-inositol phosphate. It has been shown169-170 that the phosphate obtained by hydrolysis of liver phosphatide171 or soybean phosphatide172 is a mixture of myo-inositol 1- and 2-phosphates. A myo-inositol phosphate, of unknown constitution, was isolated173 from liver without previous hydrolysis apparently it occurs in the free state. 

The stability of mature brain phosphatidate during ischemia appears to be a consequence of a developmental change and points to an interesting peculiarity in the membrane lipid metabolism of the newborn brain. Another feature of PA is that the incorporation of C-20 4 is slightly enhanced in homogenates of anoxic newborn brain while in most lipids the labeling is markedly diminished. Diacylglycerol shows a similar tendency, whereas in phosphatidyl inositol a more sharply reduced Incorporation has been observed. 

Duration of experiment brain inorganic P to plasma inorganic brain phosphatide P to plasma inorganic brain phosphatide P to brain inorganic brain phosphatide P to iiver pbosi atide... 

An abrupt change in rate of renewal of brain phosphatides occurs in the central nervous system of the rat during its growth from 30 to 50 g. As growth proceeds beyond 50 g., activity of brain phosphatides decreases throughout the central nervous system, but at a much lower rate than observed between birth and the age when the weight of 50 g. is attained. The spinal cord in the 200-g. rat possesses an activity of 20% of that of the 50-g. 

At all intervals the highest values for deuterium content were observed in liver phosphatides. The smallest incorporation of deuterium was observed in brain phosphatides, and thus the result obtained was similar to results of the incorporation of into phosphatides of different organs. The observation that plasma phosphatides have lower deuterium values than liver at the end of six hours was interpreted as suggesting incorporation of deuterated fatty acids into liver phosphatide. A similar conclusion was drawn concerning incorporation of phosphate into the phosphatide molecule (see page 156). 

The expected incorporation of mi/o-inositol into phospholipids has been observed in two31 126 and in kidney preparations in vitro,138 and some progress has been made toward understanding the enzymic mechanism involved.101 1 138,139 It appears that the inositol is neither phosphorylated nor converted to a coenzyme prior to incorporation. Hokin and Hokin140 have made the interesting observation that the turnover of myo-inositol in the monophosphoinositide of brain and pancreas slices is stimulated by acetylcholine. The effects of various drugs on this turnover have been studied by other workers. It has been postulated that the decomposition and resynthesis of inositol phosphatide is a part of the membrane-transport process.140... 

Folch, J. (1942) Brain cephalin, a mixture of phosphatides. Separation from it of phosphatidyl serine, phosphatidyl ethanolamine and a fraction containing an inositol phosphatide, J. Biol. Chem. 146, 35-44. 

The use of AIF41 in the investigation of canine cerebral cortex [40] led to the discovery of a previously unrecognized signaling pathway in the brain. These experiments demonstrated that muscarinic acetylcholine receptor-G-protein uses PLD as the effector enzyme. AlF41 caused a two- to three-fold increase in breakdown of phosphatidylcholine and rapid accumulation of choline and phosphatidic acid was observed. 

Figure 1. Schematic representation of the brain inositol signaling system. The quantities of IMPase isoenzymes and IPPase are increased by chronic lithium treatment occurring at either the gene or protein levels. Inositol in this diagram indicates the myo-inositol isomer. Calbindin -calcium binding protein DAG- diacyl glycerol Gq-GTP binding protein IMPase 1 — inositol mono phosphatase 1 IPPase- inositol polyphosphate 1-phosphatase Ins(l)P, Ins(3)P, Ins(4)P-inos-itol monophosphates Ins(l,3)P2 - inositol 1,3-bisphosphate Ins( 1,4)/ 2 - inositol 1,4-bisphos-phate Ins(3,4)/)2- inositol 3,4-bisphosphate Ins (1,4,5)P3 - inositol 1,4,5-trisphosphate Ins( 1,3,4)/ 3 - inositol 1,3,4-trisphosphate Li+-lithium PA - phosphatidic acid PI- phosphatidyl inositol PIP- phosphatidyl inositol 4-phosphate PIP2- phosphatidyl inositol 4,5-bisphosphate PIP3- phosphatidyl inositol 3,4,5 trisphosphate PLC - phospholipase-C, VPA-valproate.

Burstein and Hunter (1995) observed that THC stimulated the biosynthesis of anandamide in neuroblastoma cells employing either ethanolamine or arachidonic acid as the label. Anandamide bios5mthesis has also been shown to occur in primary cultures of rat brain neurons labelled with [H]-ethanolamine when stimulated with ionomycin, a Ca ionophore (Di Marzo et al. 1994). These authors proposed an alternate model for the biosynthesis of anandamide in which N-arachidonoyl phosphatidyl ethanolamine is cleaved by a phospholipase D activity to yield phosphatidic acid and ararchidonoylethanolamide. This model is based upon extensive studies undertaken by Schmid and collaborators (1990), who have shown that fatty acid ethanolamide formation results from the N-acylation of phosphatidyl ethanolamine by a transacylase to form N-acyl phosphatidylethanolamine. Possibly resulting from postmortem changes, this compound is subsequently hydrolyzed to the fatty acid ethanolamide and the corresponding phosphatide by a phosphodiesterase, phospholipase D. 

II Phosphatidic acid- Testis, brain Intracellular 98 kDa PA, PE Catalytic center 16... 

In addition to membrane-bound PLAiS, mammals have cytosolic PLAjS. Cytosolic PLAi activities have been studied in various tissues including heart, brain and testis. PA-PLAi has been purified from brain [45] and testes [39, 46]. Like other lipolytic enzymes, PLAi is affected by the assay conditions. Using a mixed micelle system Glomset and his colleagues [46] found that a 110 kDa enzyme from testes preferentially hydrolyzed phosphatidic acid. They cloned the PA-PLAi from bovine [16]. This PLAi lacks sequence similarity to type I PLAi, lysophospholipase, LCAT, and triacylglycerol lipases. 

The lipid composition of the brain varies slightly depending on the particular section of the brain studied (Table 1). The white matter of the brain consists primarily of myelinated neurons and myelin is predominantly sphingolipid (e.g., sphingomyelin) and cholesterol (Fig. 1). The fatty acid composition of myelin is mostly saturated and contains relatively little DHA. The gray matter of the brain, on the other hand, has very little myelin and the phosphatides PS, PE, and PI of the active neuronal membranes make up the bulk of the lipid (Salem, et al., 1986). These lipids are very unsaturated and DHA and AA are the predominant building blocks thereof. 

Helmkamp (1980b) studied the phosphatidylinositol-specific exchange protein from bovine brain. The incorporation of phosphatidic acid, phosphatidylserine, or phosphatidylglycerol into small unilamellar acceptor vesicles had little effect on the transfer of phosphatidylinositol from microsomes. However, when stearylamine was incorporated into the vesicles, the rate of transfer was decreased. A two- to fourfold stimula-... 

Myelin is approximately 75% lipid and 25% protein. Carbohydrate residues are associated with both the lipid and the protein components of myelin. High proportions of cholesterol, phospholipid, and glycolipid are found in the lipid fractions. Phospholipids include ethanolamine phosphatides, phosphatidylserine, and phosphatidylinositol glycolipids include both neutral (cerebroside, sulfatide, galactosyldiglyceride) and polar (gangliosides, especially GMj and GMJ lipids. A classification and discussion of the metabolism of brain lipids is beyond the scope of this article readers are referred to Lajtha (1969), Davison (1968), Awasthi and Srivastava (1980), and Suzuki (1981). 

J. L. W. Thudichum, Researches on the Chemical Constitution of the Brain, Report of the Medical Officer of the Privy Council, London, 1874 (cited by H. Thierfelder and E. Klenk, Die Chemie der Cerebroside und Phosphatide, Springer Verlag, Berlin, 1930). 

Hokin, L. E. and Hokin, M. R. (1958) Acetylcholine and the exchange of phosphate in phosphatidic acid in brain microsomes. J. biol. Chem., 233, 822-826. 

Kelecin Granules tin. Phosphatide found in all living organisms (plants and animals). Significant constituent of nervous tissue and brain substance. A mixture of the diglycerides of slearic, palmitic, and oleic acids, linked to the choline ester or phosphoric add. Commerda] grades contain 2.2% P. Isoln from eggs Sinclair, Can. J. Res. 26B, 777 (1948). 

Sphingomyelins, Rowamydin. Sphiugosine phosphatide occurring in the myelin sheaths of nerves. Prepn of beef heart sphingomyelin Rapport, Lerner, J. Biot. Chem. 232, 63 (1958). Isoln from human and rat brain Hausheer... 

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