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 sythesised 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.
- Bretscher, MS. (1972). Asymmetrical lipid bilayer structure for biological membranes. Nature New Biology 236:11-12.
- Lodish, H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J. (2004). Molecular Cell Biology, 5th, New York: WH Freeman.
- Castegna A, Lauderback CM, Mohmmad-Abdul H, Butterfield DA. (2004). Modulation of phospholipid asymmetry in synaptosomal membranes by the lipid peroxidation products, 4-hydroxynonenal and acrolein: implications for Alzheimer's disease. Brain Res 1004(1-2):193-7.
- Mohmmad Abdul H, Butterfield DA. (2005). Protection against amyloid beta-peptide (1-42)-induced loss of phospholipid asymmetry in synaptosomal membranes by tricyclodecan-9-xanthogenate (D609) and ferulic acid ethyl ester: implications for Alzheimer's disease. Biochim Biophys Acta 1741(1-2):140-8.
- UMich Orientation of Proteins in Membranes families/superfamily-18 - Positions of lipid flippases in membranes
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