Flippase

They are responsible for aiding the movement of phospholipid molecules between the two layers, or leaflets, that compose the membrane (transverse diffusion, also known as a "flip-flop" transition).

[4] The reason is that the polar head groups of phospholipid molecule cannot pass easily through the hydrophobic center of the bilayer, limiting their diffusion in this dimension.

[5] The possibility of active maintenance of an asymmetric distribution of molecules in the phospholipid bilayer was predicted in the early 1970s by Mark Bretscher.

The loss of asymmetry, in particular the appearance of the anionic phospholipid phosphatidylserine on the exoplasmic face, can serve as an early indicator of apoptosis[8] and as a signal for efferocytosis.

[5] Finally, a C-terminal autoregulatory domain has been identified, whose function differs between yeast and mammalian P4-type flippases.

[12] In order to bind specific lipid on the outer layer of membrane, P4-type flippase needs to be phosphorylated by ATP on its P-domain.

As the phospholipid dissociates from the complex, a conformational change on flippase occurs from E2 back to E1 readying it for the next cycle of lipid transportation.

Dephosphorylation of the P-domain is energetically coupled to translocation of the polar phospholipid head across the membrane leaflets.