Preferential incorporation of shorter and less unsaturated acyl phospholipids into high density lipoprotein-like particles in the ABCA1- and ABCA7-mediated biogenesis with apoA-I

• Lipidomix analysis was carried out for the reaction of HDL biogenesis mediated by ABCA1 with a reference to the ABCA7-mediated reaction.
• Preferential incorporation of phospholipid with shorter acyl chain length was observed from cell membrane to discoidal HDL-like particles assembled with apolipoprotein A-I.
• Preferential incorporation of phospholipid with less unsaturated acyl chains was observed for PC but not SPM.
• These preferences are most likely fluidity and mobility of the acyl chains of the phospholipid molecules.

Molecular species of phosphatidylcholine (PC) and sphingomyelin (SPM) were globally analyzed for lipidomics in the nascent high-density lipoprotein (HDL)-like particles generated with human apolipoprotein A-I (apoA-I) form HEK293 cells where either human ATP binding cassette transporter (ABC) A1 or ABCA7 was transfected and overexpressed. SPM/PC ratio was higher in the ABCA1-mediated HDL than ABCA7-mediated HDL likely being related to their cholesterol content, while it was less than the ratio in the cell membrane in either case. Molecular species composition of hydrocarbon chain moiety in each phospholipid in the HDL largely reflected that in the cells the lipoprotein originated in, without remarkable difference between ABCA1 and ABCA7. Further analysis, however, revealed apparent preference for the molecules with shorter hydrocarbon chain length for both PC and SPM in their relative incorporation into HDL by ABCA1 and ABCA7. Likewise, it was in favor for less-unsaturated hydrocarbon chains of PC while this preference was not apparent for SPM. The results are consistent with the view that assembly of HDL particles with extracellular apoA-I is primarily with the cellular phospholipid molecules being regulated in part by their physicochemical nature.