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An example of an ATP-dependent flippase in the ABC transporter family, isolated from C. jejuni. The two polypeptide chains in the homodimer structure are shown in red and blue. The extracellular surface is oriented at the top of the image and the ATP-binding domains are located at the bottom, on the cytosolic side.[1]

Flippases (rarely spelled flipases) are transmembrane lipid transporter proteins located in the membrane responsible for aiding the movement of phospholipid molecules between the two leaflets that compose a cell's membrane (transverse diffusion, also known as a "flip-flop" transition). The possibility of active maintenance of an asymmetric distribution of molecules in the phospholipid bilayer was predicted in the early 1970s by Mark Bretscher.[2][3] 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. Some flippases - often instead called scramblases[1] - are energy-independent and bidirectional, causing reversible equilibration of phospholipid between the two sides of the membrane, whereas others are energy-dependent and unidirectional, using energy from ATP hydrolysis to pump the phospholipid in a preferred direction.[4] Flippases are described as transporters that move lipids from the exoplasmic to the cytosolic face, while floppases transport in the reverse direction.[1]

Many cells maintain asymmetric distributions of phospholipids between their cytoplasmic and exoplasmic membrane leaflets.[5] 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.[6] 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.[7]

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  1. ^ a b c Hankins, Hannah M.; Baldridge, Ryan D.; Xu, Peng; Graham, Todd R. (January 2015). "Role of Flippases, Scramblases and Transfer Proteins in Phosphatidylserine Subcellular Distribution". Traffic 16 (1): 35–47. doi:10.1111/tra.12233. 
  2. ^ Bretscher, Mark S. (1 March 1972). "Asymmetrical Lipid Bilayer Structure for Biological Membranes". Nature New Biology 236 (61): 11–12. doi:10.1038/newbio236011a0. PMID 4502419. 
  3. ^ Bretscher, Mark (1974). "Some Aspects of Membrane Structure". In Estrada-O., Sergio; Gitler, Carlos. Perspectives in membrane biology first Mexican Society of Biochemistry symposium. New York: Academic Press. pp. 3–24. ISBN 9780323143592. 
  4. ^ Holthuis, Joost CM, and Levine, T.P.,"Lipid traffic: floppy drives and a superhighway." Nature reviews Molecular cell biology 6.3 (2005): 209-220.[1]
  5. ^ 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.
  6. ^ 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.
  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.

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