Flippase
Encyclopedia
Flippases are a family of transmembrane lipid transporter enzyme
s 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 cytoplasm
ic 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 neuron
s as a response to exposure to amyloid beta
peptides, thought to be a primary cause of the neurodegenerative effects of Alzheimer's disease
.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s located in the membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
responsible for aiding the movement of phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
molecules between the two leaflets that compose a cell's membrane (transverse diffusion). Their existence was predicted in 1972 by Mark Bretscher
Mark Bretscher
Mark Bretscher is a British biological scientist and Fellow of the Royal Society. He works at the Medical Research Council Laboratory of Molecular Biology in Cambridge, United Kingdom...
, 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
Chemical polarity
In chemistry, polarity refers to a separation of electric charge leading to a molecule or its chemical groups having an electric dipole or multipole moment. Polar molecules interact through dipole–dipole intermolecular forces and hydrogen bonds. Molecular polarity is dependent on the difference in...
head groups cannot pass easily through the hydrophobic center of the bilayer, limiting their diffusion in this dimension. Phospholipid molecules that are synthesized
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
in the cell are incorporated into the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
ic face of the membrane, where flippases can transfer them to the exoplasmic face. Energy-dependent flippases require energy input in the form of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
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
Phosphatidylserine
Phosphatidylserine is a phospholipid component, usually kept on the inner-leaflet of cell membranes by an enzyme called flippase...
on the exoplasmic face, can serve as an early indicator of apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. This effect has been observed in neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s as a response to exposure to amyloid beta
Amyloid beta
Amyloid beta is a peptide of 36–43 amino acids that is processed from the Amyloid precursor protein. While it is most commonly known in association with Alzheimer's disease, it does not exist specifically to cause disease...
peptides, thought to be a primary cause of the neurodegenerative effects of Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.