Which enzyme is responsible for flipping lipids between membrane leaflets?
Movement of intact phospholipid with polar headgroup across hydrophobic core has activation energy exceeding 60 kJ per mol, making spontaneous flip-flop negligible within hours to days, so cells require dedicated translocase catalysts. Flippases are P-type P4-ATPases, ten members in mammals, that adopt E1-E2 conformational cycle phosphorylating conserved aspartate to translocate fluorescent NBD-labeled aminophospholipids from exoplasmic to cytoplasmic leaflet against concentration gradient at expense of ATP, maintaining phosphatidylserine inside. Floppases belong to ABC transporter family also
Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 10: Flippases, Floppases, Scramblases.
