173f08bae7414dd3029c33295b16e194 pmc_10138509.pdf cbe49e146b9a45ab7b5fc78a511fd2730c60bb65 pmc_10138509.pdf 7169debaceb9ecac4e153f1b43d02ef3e4b8a77ed8fa46e170c0594616f50cfa pmc_10138509.pdf Title: Can Electronegative LDL Act as a Multienzymatic Complex? Subject: Electronegative LDL (LDL(-)) is a minor form of LDL present in blood for which proportions are increased in pathologies with increased cardiovascular risk. In vitro studies have shown that LDL(-) presents pro-atherogenic properties, including a high susceptibility to aggregation, the ability to induce inflammation and apoptosis, and increased binding to arterial proteoglycans; however, it also shows some anti-atherogenic properties, which suggest a role in controlling the atherosclerotic process. One of the distinctive features of LDL(-) is that it has enzymatic activities with the ability to degrade different lipids. For example, LDL(-) transports platelet-activating factor acetylhydrolase (PAF-AH), which degrades oxidized phospholipids. In addition, two other enzymatic activities are exhibited by LDL(-). The first is type C phospholipase activity, which degrades both lysophosphatidylcholine (LysoPLC-like activity) and sphingomyelin (SMase-like activity). The second is ceramidase activity (CDase-like). Based on the complementarity of the products and substrates of these different activities, this review speculates on the possibility that LDL(-) may act as a sort of multienzymatic complex in which these enzymatic activities exert a concerted action. We hypothesize that LysoPLC/SMase and CDase activities could be generated by conformational changes in apoB-100 and that both activities occur in proximity to PAF-AH, making it feasible to discern a coordinated action among them. Keywords: low-density lipoprotein; modified LDL; electronegative LDL; platelet-activating factor acetylhydrolase; phospholipase C; sphingomyelinase; ceramidase; LDL aggregation; inflammation Author: Sonia Benitez, Núria Puig, José Rives, Arnau Solé and José Luis Sánchez-Quesada Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Apr 11 17:34:24 2023 CEST ModDate: Tue Apr 11 17:40:24 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 782369 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CIQLLF+VnURWPalladioL Type 1 Custom yes yes no 10 0 FWGCYD+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 FKGOMQ+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 VPVIMD+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 FXXUVH+CMSY10 Type 1 Builtin yes yes no 28 0 YUQEMP+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 50 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 53 0 QDCWHF+EURM10 Type 1 Builtin yes yes no 78 0 KHGIOA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 103 0 KHGIOB+PalatinoLinotype CID TrueType Identity-H yes yes yes 106 0 KHGIOC+PalatinoLinotype TrueType WinAnsi yes yes no 112 0 KHGIPE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 115 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-01-30 02:34:17 CET RepresentationInformation: pmc_10138509.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-08-01 02:31:36 CEST Size: 782369 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 422 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: LDL Modification and Atherosclerosis Destination: section.1 Item: Title: Association of LDL(-) with Disease Destination: section.2 Item: Title: Atherogenic Properties of LDL(-) Destination: section.3 Item: Title: Some Potentially Protective Properties of LDL(-) Destination: section.4 Item: Title: Structural Alterations in LDL(-) Destination: section.5 Item: Title: Enzymatic Activities Associated with LDL(-) Destination: section.6 Item: Title: Origin of PLC-Like and CDase-Like Activities Associated with LDL(-) Destination: section.7 Item: Title: Could the Enzymatic Activities Associated with LDL(-) Act Cooperatively as a sort of Enzymatic Complex? Destination: section.8 Item: Title: Conclusions Destination: section.9 Item: Title: References Destination: section.10 Info: Title: Can Electronegative LDL Act as a Multienzymatic Complex? Author: Sonia Benitez, Núria Puig, José Rives, Arnau Solé and José Luis Sánchez-Quesada Subject: Electronegative LDL (LDL(-)) is a minor form of LDL present in blood for which proportions are increased in pathologies with increased cardiovascular risk. In vitro studies have shown that LDL(-) presents pro-atherogenic properties, including a high susceptibility to aggregation, the ability to induce inflammation and apoptosis, and increased binding to arterial proteoglycans; however, it also shows some anti-atherogenic properties, which suggest a role in controlling the atherosclerotic process. One of the distinctive features of LDL(-) is that it has enzymatic activities with the ability to degrade different lipids. For example, LDL(-) transports platelet-activating factor acetylhydrolase (PAF-AH), which degrades oxidized phospholipids. In addition, two other enzymatic activities are exhibited by LDL(-). The first is type C phospholipase activity, which degrades both lysophosphatidylcholine (LysoPLC-like activity) and sphingomyelin (SMase-like activity). The second is ceramidase activity (CDase-like). Based on the complementarity of the products and substrates of these different activities, this review speculates on the possibility that LDL(-) may act as a sort of multienzymatic complex in which these enzymatic activities exert a concerted action. We hypothesize that LysoPLC/SMase and CDase activities could be generated by conformational changes in apoB-100 and that both activities occur in proximity to PAF-AH, making it feasible to discern a coordinated action among them. 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