Gamma-hydroxyalkenals are oxidatively cleaved through Michael addition of acylperoxy radicals and fragmentation of intermediate beta-hydroxyperesters.
Oxidative cleavage of arachidonate (C(20)) and linoleate (C(18)) phospholipids generates truncated C(8) or C(12) gamma-hydroxyalkenal phospholipids as well as C(5) or C(9) carboxyalkanoate phospholipids, which are abundant in atherosclerotic plaques. The gamma-hydroxyalkenals promote foam cell formation by scavenger receptor CD36-mediated endocytosis. The carboxyalkanoates are potent regulators of endothelial cell functions that may promote atherogenesis. We now report an unexpected biosynthetic interconnection; the carboxyalkanoates can be generated through oxidative cleavage of the gamma-hydroxyalkenals with the loss of three carbons. This unprecedented transformation is shown to involve Michael addition of an acylperoxy radical and fragmentation of the resulting beta-hydroxyperester.
Balamraju
Yuvaraju N
YN
Contribution from the Department of Chemistry, Case Western Reserve University, Cleveland, OH 44107-7078, USA.
Sun
Mingjiang
M
Salomon
Robert G
RG
D000096:Acetone / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism; D000475:Alkenes / Q000737:chemistry* / Q000378:metabolism; D004952:Esters / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D009829:Oleic Acids / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D010422:Pentanones / Q000737:chemistry; D010545:Peroxides / Q000737:chemistry; D010659:Phenylhydrazines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism
C107324:10-hydroxy-8-octadecenoic acid; D000447:Aldehydes; D000475:Alkenes; D004952:Esters; D005609:Free Radicals; D009829:Oleic Acids; D010422:Pentanones; D010545:Peroxides; D010659:Phenylhydrazines; D010743:Phospholipids; C030299:phenylhydrazine; D010767:Phosphorylcholine; D000096:Acetone; C049375:perhydroxyl radical; C057461:1-pentene-3-one