Biosynthesis Of Endosome-Specific Lipid Bis(Monoacylglycero)Phosphate

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dc.contributor.authorLim, Shi Rou
dc.date.accessioned2019-04-30T07:39:09Z
dc.date.available2019-04-30T07:39:09Z
dc.date.issued2018-03
dc.description.abstractThe hypothetical de novo biosynthetic pathway of endosome-specific phospholipid, bis(monoacylglycero)phosphate (BMP) from endogenous phosphatidylglycerol (PG) precursor via lysophosphatidylglycerol (LPG) intermediate had been considered. In the present study, an alternative BMP biosynthetic route from PG via acylphosphatidylglycerol (AcPG) intermediate was proposed. A considerable amount of AcPG was found present in and outside the RAW 264.7 cells during 24 hours of incubation with exogenous PG. A transacylase is required to transfer an acyl chain from a PG donor to a PG acceptor, transforming the acceptor PG into AcPG and the donor PG into LPG. To complete the BMP biosynthesis following the AcPG route, a reorientation step of the diacylated glycerol moiety has to occur with concomitant loss of an acyl residue. The new pathway of PG conversion to BMP via AcPG forming transacylase activity was established by an original in vitro assay utilizing fetal bovine serum (FBS) as enzymatic source. A phospholipase A1 displaying a transacylase activity was revealed by utilizing asymmetric PO PG as acceptor and donor, yielding a PO-P AcPG:PO-O AcPG ratio of 10:1. This transacylase activity was further characterized in terms of divalent ions, pH and substrate specificity. In vitro experiments utilizing the secreted enzyme complex from RAW 264.7 cells grown under starvation conditions indicated that both proposed enzymatic activities, transacylase and reorientation, were present. At intermediate time points, the combined amount of PG, BMP and AcPG was significantly less compared to the amount of supplied PG at the beginning or the total BMP amount produced after 24 hours of incubation. An elevation in triacylglycerol amount in the cell after 8 hours of incubation indicated that PG could be converted to triacylglycerol via diacylglycerol to store temporarily the excessive amount of fatty acids provided to the cells.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/8128
dc.language.isoenen_US
dc.publisherUniversiti Sains Malaysiaen_US
dc.subjectBiosynthesis of endosome-specific lipiden_US
dc.subjectbis monoacylglycero phosphateen_US
dc.titleBiosynthesis Of Endosome-Specific Lipid Bis(Monoacylglycero)Phosphateen_US
dc.typeThesisen_US
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