The metabolism of glycerophospholipid and its regulation in monocytes and macrophages

Nakagawa, Yasuhito; Waku, Keizo

doi:10.1016/0163-7827(89)90013-1

Cited by 41 publications

(33 citation statements)

References 272 publications

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“…Arachidonic acid liberated by PLA 2 s is converted to eicosanoids (9,28). Lysophospholipids are also precursors for a different class of lipid mediators including PAF, LPA, and endocannabinoids (29)(30)(31)(32)(33)(34)(35) (Fig.…”

Section: Discussionmentioning

confidence: 99%

Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity

Hishikawa

Shindou²,

Kobayashi³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

282

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All organisms consist of cells that are enclosed by a cell membrane containing bipolar lipids and proteins. Glycerophospholipids are important not only as structural and functional components of cellular membrane but also as precursors of various lipid mediators. Polyunsaturated fatty acids comprising arachidonic acid or eicosapentaenoic acid are located at sn-2 position, but not at sn-1 position of glycerophospholipids in an asymmetrical manner. In addition to the asymmetry, the membrane diversity is important for membrane fluidity and curvature. To explain the asymmetrical distribution of fatty acids, the rapid turnover of sn-2 position was proposed in 1958 by Lands [Lands WE (1958) Metabolism of glycerolipides: A comparison of lecithin and triglyceride synthesis. J Biol Chem 231:883-888]. However, the molecular mechanisms and biological significance of the asymmetry remained unknown. Here, we describe a putative enzyme superfamily consisting mainly of three gene families, which catalyzes the transfer of acyl-CoAs to lysophospholipids to produce different classes of phospholipids. Among them, we characterized three important enzymes with different substrate specificities and tissue distributions; one, termed lysophosphatidylcholine acyltransferase-3 (a mammalian homologue of Drosophila nessy critical for embryogenesis), prefers arachidonoyl-CoA, and the other two enzymes incorporate oleoyl-CoAs to lysophosphatidylethanolamine and lysophosphatidylserine. Thus, we propose that the membrane diversity is produced by the concerted and overlapped reactions with multiple enzymes that recognize both the polar head group of glycerophospholipids and various acyl-CoAs. Our findings constitute a critical milestone for our understanding about how membrane diversity and asymmetry are established and their biological significance.glycerophospholipids ͉ Lands' cycle ͉ membrane remodeling ͉ phospholipase A 2 ͉ acyl-CoA

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Section: Discussionmentioning

confidence: 99%

Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity

Hishikawa

Shindou²,

Kobayashi³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

282

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“…PLA 2 Enzyme Activities SB 203347 and AACOCF 3 were assessed for their effects on human monocyte subcellular fraction 85-kDa PLA 2 or 14-kDa PLA 2 enzyme activities as described under "Experimental Procedures." These results were compared to the effects of these compounds on purified rh PLA 2 enzymes.…”

Section: The Effect Of 85-or 14-kda Pla 2 Inhibition On Monocytementioning

confidence: 99%

“…In drug studies, cells were pretreated with dimethyl sulfoxide (Me 2 SO, Ͻ1%) vehicle or appropriate concentrations of AACOCF 3 Prostaglandin E 2 , PGD 2 , TXB 2 , 6-keto-PGF 2␣ , LTB 4 , or LTC 4 were directly measured in cell-free medium using enzyme immunoassay kits purchased from Cayman Chemical Co. as described previously. Data were expressed as picograms or nanograms/ml of sample.…”

Section: Measurement Of Stimuli-induced Eicosanoid Release-monocytesmentioning

confidence: 99%

“…More direct evidence for a role in prostanoid formation has been obtained through selective inhibitors of the 85-kDa PLA 2 activity or modulation of enzyme levels by antisense oligonucleotides (18 -21). Arachidonyl trifluoromethyl ketone (AACOCF 3 ), a slow, tight-binding inhibitor of 85-kDa PLA 2 , reduces stimulated AA release from platelets, U937 monocytes, and mesangial cells and subsequent platelet thromboxane (TXB 2 ) and 12 hydroxyeicosatetraenoic acid biosynthesis (18 -20). AACOCF 3 is selective with respect to other PLA 2 enzymes and does not have an effect on CoAindependent transacylase (18).…”

mentioning

confidence: 99%

“…Much work has been directed toward understanding the liberation of arachidonic acid (AA) 1 from human monocyte phospholipids (PL) and its subsequent metabolism to a number of cyclooxygenase (COX) and 5-lipoxygenase (5-LO) products (1)(2)(3)(4). The first rate-limiting enzyme in eicosanoid formation is phospholipase A 2 (PLA 2 , EC 3.1.1.4), which liberates AA from the sn-2 position of cellular PL (5,6).…”

mentioning

confidence: 99%

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Depletion of Human Monocyte 85-kDa Phospholipase A2 Does Not Alter Leukotriene Formation

Marshall

Bolognese

Winkler

et al. 1997

Journal of Biological Chemistry

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Human monocytes possess several acylhydrolase activities and are capable of producing both prostanoids (PG) and leukotriene (LT) products upon acute stimulation with calcium ionophore, A23187 or phagocytosis of zymosan particles. The cytosolic 85-kDa phospholipase (PLA) A 2 co-exists with the 14-kDa PLA 2 in the human monocyte, but their respective roles in LT production are not well understood. Reduction in 85-kDa PLA 2 cellular protein levels by initiation site-directed antisense (SK 7111) or exposure to the 85-kDa PLA 2 inhibitor, arachidonyl trifluoromethyl ketone (AACOCF 3 ), prevented A23187 or zymosan-stimulated monocyte prostanoid formation. In contrast, neither treatment altered stimulated LTC 4 production. This confirmed the important role of the 85-kDa PLA 2 in prostanoid formation but suggests that it has less of a role in LT biosynthesis. Alternatively, treatment of monocytes with the selective, active site-directed 14-kDa PLA 2 inhibitor, SB 203347, prior to stimulation had no effect on prostanoid formation at concentrations that totally inhibited LT formation. Addition of 20 M exogenous arachidonic acid to monocytes exposed to SK 7111 or SB 203347 did not alter A23187-induced PGE 2 or LTC 4 generation, respectively, indicating that these agents had no effect on downstream arachidonic acid-metabolizing enzymes in this setting. Taken together, these results provide evidence that the 85-kDa PLA 2 may play a more significant role in the formation of PG than LT. Further, utilization of SB 203347 provides intriguing data to form the hypothesis that a non-85-kDa PLA 2 sn-2 acyl hydrolase, possibly the 14-kDa PLA 2 , may provide substrate for LT formation.

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Compositional Differences between Preterm Milk of Different Gestational Ages with the Term Milk: A Comparative Lipidomic Study by LC‐MS/MS

Zhao

Zhang

Liu

et al. 2022

Euro J Lipid Sci & Tech

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Human milk lipids have important biological effects on recipient infants. The objective of this study is to comprehensively describe lipidomic differences between preterm milk of different gestational ages and term milk over the course of lactation. Colostrum (<5 d postpartum, n = 20 for very preterm [VPT], n = 20 for moderately preterm [MPT] and n = 30 for full-term [FT]) and mature milk (at four weeks postpartum, n = 11 for extremely preterm [EPT], n = 23 for VPT, n = 21 for MPT, and n = 25 for FT) are collected from 88 mothers who had delivered premature babies and 39 who had delivered term infants. It is found that the relative abundance of 10 out of 43 lipid subclasses are persistently higher in preterm milk than in term milk over the course of lactation. Diacylglycerol and fatty acid ester of hydroxyl fatty acid (FAHFA) lipid classes contribute most to the differences. The ten individual lipid species differing most significantly between VPT and FT colostrum are mainly part of the phosphatidylethanolamine and diacylglycerol groups. Levels of lipid species from the FAHFA class are significantly higher in both EPT and VPT mature milk than in their FT counterpart. The lipids in preterm and term milk show substantial differences, which may be critical for postnatal growth. Practical applications: These findings expand the current understanding of lipid components in human milk and provide important laboratory data for the future management of infant feeding, particularly of fragile, high risk EPT and VPT infants.

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The metabolism of glycerophospholipid and its regulation in monocytes and macrophages

Cited by 41 publications

References 272 publications

Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity

Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity

Depletion of Human Monocyte 85-kDa Phospholipase A2 Does Not Alter Leukotriene Formation

Compositional Differences between Preterm Milk of Different Gestational Ages with the Term Milk: A Comparative Lipidomic Study by LC‐MS/MS

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