Flippases (rarely, flipases) are a family of transmembrane lipid transporter enzymes located in the membrane responsible for aiding the movement of phospholipid molecules between the two leaflets that compose a cell's membrane (transverse diffusion). Their existence was predicted in 1972 by Mark Bretscher, who also named them, to explain how an asymmetric phospholipid bilayer could be formed. Although phospholipids diffuse rapidly in the plane of the membrane, their polar head groups cannot pass easily through the hydrophobic center of the bilayer, limiting their diffusion in this dimension. Phospholipid molecules that are synthesized in the cell are incorporated into the cytoplasmic face of the membrane, where flippases can transfer them to the exoplasmic face. Energy-dependent flippases require energy input in the form of ATP to carry out their function, often known as a flip-flop. However, there are energy-independent flippases that do not require the hydrolysis of ATP and are unidirectional in their action. These energy-independent flippases are responsible for transferring newly synthesised lipids from the outer to the inner leaflet of membranes.
Many cells maintain asymmetric distributions of phospholipids between their cytoplasmic and exoplasmic membrane leaflets. 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. This effect has been observed in neurons as a response to amyloid beta peptides, thought to be a primary cause of the neurodegenerative effects of Alzheimer's disease.
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