Metabolism of Molecular Species of Diacylglycerophospholipids

Holub, Bruce J.; Kuksis, A.

doi:10.1016/b978-0-12-024916-9.50007-x

Cited by 326 publications

(112 citation statements)

References 504 publications

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“…Furthermore, our findings also demon- strate that upon exposure of cerebral cortex to 65 pM substance P, there is a decrease in 18:0 content of PtdIns. These results suggest that the peptide elicits a preferential degradation of 1-stearyl-2-arachidonoylglycerophosphoinositol, described as major molecular species in the brain [25]. Such a suggestion is supported by the increase observed in both 16: 0 and 18: 1 in PtdIns.…”

Section: Discussionsupporting

confidence: 73%

Dual mechanism of phosphatidylinositol hydrolysis by substance P in brain

Catalán¹,

Martı́nez²,

Aragonés³

et al. 1988

European Journal of Biochemistry

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The treatment of cerebral cortex slices with substance P caused alterations in the phospholipid levels. A significant loss of phosphatidylinositol in a dose-dependent manner was observed. In contrast, the levels of the major phospholipids, phosphatidylcholine and phosphatidylethanolamine, were enhanced by the peptide.The effect of substance P on the fatty acid composition of phospholipids was also studied. The most relevant event was the decrease in the content of both stearic and arachidonic acids of phosphatidylinositol. This decrease was more evident at the lowest substance P concentration tested (65 pM).These results are consistent with the phosphatidylinositol breakdown caused by substance P in some tissues. Furthermore, our data indicate that this breakdown is selective depending on the peptide dose. Thus, in the presence of very low doses of substance P (65 pM) a preferential degradation of 1 -acyl(predominantly stearoy1)-2-arachidonoylglycerophosphoinositol molecular species occurs, whereas high doses of the peptide (0.65 pM) induce a generalized hydrolysis of phosphatidylinositol without showing any preference towards molecular species rich in arachidonic acid.Hence we describe for the first time a dual, dose-dependent mechanism for phosphatidylinositol hydrolysis by substance P, suggesting the possibility that either phospholipase A2 or phospholipase C activation is involved.Substance P is an endogenous peptide widely distributed throughout the mammalian nervous system. Many effects evoked by the peptide have been reviewed [l] but the effect of substance P on lipid metabolism has not been studied in detail and this particular area is far from being fully understood. In this respect some investigations have documented that substance P is able to induce hydrolysis of inositol phospholipids in some tissues [2 -111. Recently we have demonstrated [12] in rat cerebral cortex an increase of the ratio cholesterol/phospholipid induced by substance P. Furthermore, our study demonstrates that substance P caused a decrease on both linoleic and arachidonic acids in total phospholipids, whereas the saturated and monounsaturated fatty acids were enhanced. Thus, substance P seems to modify the hydrophobic moiety of phospholipids.On the other hand there are several reports demonstrating that agonists which cause the breakdown of inositol phospholipids also evoke a release of free arachidonic acid (20:4) from esterified lipids [13,14]. Two pathways have been Correspondence to R. E. Catalan,

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Section: Discussionsupporting

confidence: 73%

Dual mechanism of phosphatidylinositol hydrolysis by substance P in brain

Catalán¹,

Martı́nez²,

Aragonés³

et al. 1988

European Journal of Biochemistry

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“…The combination of two acyl chains at sn-1 and sn-2 positions generates diverse and distinct profi les of DG species. In this respect DG derived from PI is shown to be largely composed of polyunsaturated acyl chains, i.e., 1-stearoyl-2-arachidonoyl species, whereas PC-derived DG contains mono-unsaturated and saturated acyl chains (Holub and Kuksis 1978). The extent to which particular DG species contribute to the signaling is uncertain, although there is some preference for polyunsaturated DG species with regard to PKC activation: Saturated DGs are generally poor activators, di-unsaturated DG more active, and polyunsaturated DGs, such as 1-stearoyl-2-arachidonoyl DG, most potent (Marignani et al 1996;Schachter et al 1996).…”

Section: Characteristics Of Diacylglycerolmentioning

confidence: 99%

“…One possibility is that arachidonoyl-specifi c DGKε may attenuate specifi cally the signal of arachidonoyl-DG derived mostly from the breakdown of PI, although the other isozymes are also capable of catalyzing arachidonoyl-DG nonspecifi cally (Holub and Kuksis 1978). Alternatively, if DGKε works specifi cally on the arachidonatecontaining species of DG, multiple cycles of this pathway would progressively enrich PI with arachidonate (Prescott and Majerus 1981;Glomset 1996).…”

Section: Substrate Specifi City Of Diacylglycerol Kinasementioning

confidence: 99%

Lipid Messenger, Diacylglycerol, and its Regulator, Diacylglycerol Kinase, in Cells, Organs, and Animals: History and Perspective

Goto

Hozumi

Nakano

et al. 2008

Tohoku J. Exp. Med.

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Diacylglycerol kinase (DGK) metabolizes diacylglycerol (DG), a glycerolipid containing two acyl chains, to convert phosphatidic acid. DG is produced through phosphoinositide turnover within the membrane and is well known to act as a second messenger that modulates the activity of protein kinase C in the cellular signal transduction. Recent studies have revealed that DG also activates several proteins, including Ras guanine-nucleotide releasing protein and ion channels such as transient receptor potential proteins. Therefore, DGK is thought to participate in a number of signaling cascades by modulating levels of DG. Previous studies have disclosed that DGK is composed of a family of the isozymes, which differ in the structure, enzymological property, gene expression and localization, subcellular localization, and binding molecules. The present review focuses on the stories of phosphoinositide turnover and DG, including historical views, structural features, metabolism, and relevant cellular phenomena, together with the characteristics of DGK isozymes and the pathophysiological fi ndings on animal studies using knockout mice and models for human diseases. Now it is being revealed that the structural and functional diversity and heterogeneity of and around DGK support the proper arrangement of the complex signal transduction machinery.phosphoinositide; diacylglycerol; second messenger; diacylglycerol kinase; isozyme; animal models. Tohoku

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“…Various kinds of fatty acids are distributed in membrane phospholipids in mammalian cells and tissues (Lands and Crawford, 1976;Holub and Kuksis, 1978;MacDonald and Sprecher, 1991). The fatty acyl residues of individual phospholipids seem to be under strict metabolic regulation.…”

Section: Introductionmentioning

confidence: 99%

Caenorhabditis elegans mboa-7, a Member of the MBOAT Family, Is Required for Selective Incorporation of Polyunsaturated Fatty Acids into Phosphatidylinositol

Lee

Inoué

Imae

et al. 2008

MBoC

122

117

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Phosphatidylinositol (PI) is a component of membrane phospholipids, and it functions both as a signaling molecule and as a compartment-specific localization signal in the form of polyphosphoinositides. Arachidonic acid (AA) is the predominant fatty acid in the sn-2 position of PI in mammals. LysoPI acyltransferase (LPIAT) is thought to catalyze formation of AA-containing PI; however, the gene that encodes this enzyme has not yet been identified. In this study, we established a screening system to identify genes required for use of exogenous polyunsaturated fatty acids (PUFAs) in Caenorhabditis elegans. In C. elegans, eicosapentaenoic acid (EPA) instead of AA is the predominant fatty acid in PI. We showed that an uncharacterized gene, which we named mboa-7, is required for incorporation of PUFAs into PI. Incorporation of exogenous PUFA into PI of the living worms and LPIAT activity in the microsomes were greatly reduced in mboa-7 mutants. Furthermore, the membrane fractions of transgenic worms expressing recombinant MBOA-7 and its human homologue exhibited remarkably increased LPIAT activity. mboa-7 encodes a member of the membrane-bound O-acyltransferase family, suggesting that mboa-7 is LPIAT. Finally, mboa-7 mutants had significantly lower EPA levels in PI, and they exhibited larval arrest and egg-laying defects. INTRODUCTIONVarious kinds of fatty acids are distributed in membrane phospholipids in mammalian cells and tissues (Lands and Crawford, 1976;Holub and Kuksis, 1978;MacDonald and Sprecher, 1991). The fatty acyl residues of individual phospholipids seem to be under strict metabolic regulation. In general, saturated fatty acids are esterified at the sn-1 position, whereas polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA), are commonly found at the sn-2 position. Three-fourths or more of the phosphatidylinositol (PI) fraction in rat liver and brain constitutes the 1-stearoyl-2-arachidonoyl species (Holub and Kuksis, 1971;Baker and Thompson, 1972). In contrast, the total pool of precursor phosphatidic acid (PA) in rat liver and brain has a fatty acid composition that does not resemble that of PI, showing a low AA content (Possmayer et al., 1969;Akesson et al., 1970;Baker and Thompson, 1972). Selectivity could be expressed during de novo synthesis at the level of formation of cytidine 5Ј-diphosphate (CDP)-diacylglycerol from PA and cytidine 5Ј-triphosphate or in the use of CDP-diacylglycerol in the final reaction. In fact, CDP-diacylglycerol synthase, which prefers 1-stearoyl-2-arachidonoyl PA as a substrate in vitro, has been cloned, although expression is restricted to testis, retina, and brain (Saito et al., 1997).An alternative mechanism for species selection has been proposed on the basis of turnover studies in rat brain in vivo (Baker and Thompson, 1972). [ 3 H]AA and [ 14 C]glycerol injected intracerebrally were incorporated almost exclusively into brain phospholipids. Comparison of PI and PA radioactivity suggest that the initial flux of AA into PI was independent of de novo synthesi...

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Metabolism of Molecular Species of Diacylglycerophospholipids

Cited by 326 publications

References 504 publications

Dual mechanism of phosphatidylinositol hydrolysis by substance P in brain

Dual mechanism of phosphatidylinositol hydrolysis by substance P in brain

Lipid Messenger, Diacylglycerol, and its Regulator, Diacylglycerol Kinase, in Cells, Organs, and Animals: History and Perspective

Caenorhabditis elegans mboa-7, a Member of the MBOAT Family, Is Required for Selective Incorporation of Polyunsaturated Fatty Acids into Phosphatidylinositol

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