Facilitated diffusion

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Facilitated diffusion (also known as facilitated transport or passive-mediated transport) is the process of spontaneous passive transport (as opposed to active transport) of molecules or ions across a biological membrane via specific transmembrane integral proteins. Facilitated diffusion_sentence_0

Being passive, facilitated transport does not directly require chemical energy from ATP hydrolysis in the transport step itself; rather, molecules and ions move down their concentration gradient reflecting its diffusive nature. Facilitated diffusion_sentence_1

Facilitated diffusion is different from simple diffusion in several ways. Facilitated diffusion_sentence_2

Facilitated diffusion_ordered_list_0

  1. the transport relies on molecular binding between the cargo and the membrane-embedded channel or carrier protein.Facilitated diffusion_item_0_0
  2. the rate of facilitated diffusion is saturable with respect to the concentration difference between the two phases; unlike free diffusion which is linear in the concentration difference.Facilitated diffusion_item_0_1
  3. The temperature dependence of facilitated transport is substantially different due to the presence of an activated binding event, as compared to free diffusion where the dependence on temperature is mild.Facilitated diffusion_item_0_2

Polar molecules and large ions dissolved in water cannot diffuse freely across the plasma membrane due to the hydrophobic nature of the fatty acid tails of the phospholipids that make up the lipid bilayer. Facilitated diffusion_sentence_3

Only small, non-polar molecules, such as oxygen and carbon dioxide, can diffuse easily across the membrane. Facilitated diffusion_sentence_4

Hence, small polar molecules are transported by proteins in the form of transmembrane channels. Facilitated diffusion_sentence_5

These channels are gated, meaning that they open and close, and thus deregulate the flow of ions or small polar molecules across membranes, sometimes against the osmotic gradient. Facilitated diffusion_sentence_6

Larger molecules are transported by transmembrane carrier proteins, such as permeases, that change their conformation as the molecules are carried across (e.g. glucose or amino acids). Facilitated diffusion_sentence_7

Non-polar molecules, such as retinol or lipids, are poorly soluble in water. Facilitated diffusion_sentence_8

They are transported through aqueous compartments of cells or through extracellular space by water-soluble carriers (e.g. retinol binding protein). Facilitated diffusion_sentence_9

The metabolites are not altered because no energy is required for facilitated diffusion. Facilitated diffusion_sentence_10

Only permease changes its shape in order to transport metabolites. Facilitated diffusion_sentence_11

The form of transport through a cell membrane in which a metabolite is modified is called group translocation transportation. Facilitated diffusion_sentence_12

Glucose, sodium ions, and chloride ions are just a few examples of molecules and ions that must efficiently cross the plasma membrane but to which the lipid bilayer of the membrane is virtually impermeable. Facilitated diffusion_sentence_13

Their transport must therefore be "facilitated" by proteins that span the membrane and provide an alternative route or bypass mechanism. Facilitated diffusion_sentence_14

Some examples of proteins that mediate this process are glucose transporters, organic cation transport proteins, urea transporter, monocarboxylate transporter 8 and monocarboxylate transporter 10. Facilitated diffusion_sentence_15

Various attempts have been made by engineers to mimic the process of facilitated transport in synthetic (i.e., non-biological) membranes for use in industrial-scale gas and liquid separations, but these have met with limited success to date, most often for reasons related to poor carrier stability and/or dissociation of the carrier from the passive transport. Facilitated diffusion_sentence_16

In vivo model of facilitated diffusion Facilitated diffusion_section_0

In living organisms, the main physical and biochemical processes that are required for survival are regulated by diffusion. Facilitated diffusion_sentence_17

Facilitated diffusion is one form of diffusion and it is important in several metabolic processes of living cells. Facilitated diffusion_sentence_18

One vital role of facilitated diffusion is that it is the main mechanism behind the binding of Transcription Factors (TFs) to designated target sites on the DNA molecule. Facilitated diffusion_sentence_19

The in vitro model, which is a very well known method of facilitated diffusion, that takes place outside of a living cell, explains the 3-dimensional pattern of diffusion in the cytosol and the 1-dimensional diffusion along the DNA contour. Facilitated diffusion_sentence_20

After carrying out extensive research on processes occurring out of the cell, this mechanism was generally accepted but there was a need to verify that this mechanism could take place in vivo or inside of living cells. Facilitated diffusion_sentence_21

Bauer & Metzler (2013) therefore carried out an experiment using a bacterial genome in which they investigated the average time for TF – DNA binding to occur. Facilitated diffusion_sentence_22

After analyzing the process for the time it takes for TF's to diffuse across the contour and cytoplasm of the bacteria's DNA, it was concluded that in vitro and in vivo are similar in that the association and dissociation rates of TF's to and from the DNA are similar in both. Facilitated diffusion_sentence_23

Also, on the DNA contour, the motion is slower and target sites are easy to localize while in the cytoplasm, the motion is faster but the TF's are not sensitive to their targets and so binding is restricted. Facilitated diffusion_sentence_24

Intracellular facilitated diffusion Facilitated diffusion_section_1

Single-molecule imaging is an imaging technique which provides an ideal resolution necessary for the study of the Transcription factor binding mechanism in living cells. Facilitated diffusion_sentence_25

In prokaryotic bacteria cells such as E. coli, facilitated diffusion is required in order for regulatory proteins to locate and bind to target sites on DNA base pairs. Facilitated diffusion_sentence_26

There are 2 main steps involved: the protein binds to a non-specific site on the DNA and then it diffuses along the DNA chain until it locates a target site, a process referred to as sliding. Facilitated diffusion_sentence_27

According to Brackley et al. Facilitated diffusion_sentence_28

(2013), during the process of protein sliding, the protein searches the entire length of the DNA chain using 3-D and 1-D diffusion patterns. Facilitated diffusion_sentence_29

During 3-D diffusion, the high incidence of Crowder proteins creates an osmotic pressure which brings searcher proteins (e.g. Lac Repressor) closer to the DNA to increase their attraction and enable them to bind, as well as steric effect which exclude the Crowder proteins from this region (Lac operator region). Facilitated diffusion_sentence_30

Blocker proteins participate in 1-D diffusion only i.e. bind to and diffuse along the DNA contour and not in the cytosol. Facilitated diffusion_sentence_31

Facilitated diffusion of proteins on Chromatin Facilitated diffusion_section_2

The in vivo model mentioned above clearly explains 3-D and 1-D diffusion along the DNA strand and the binding of proteins to target sites on the chain. Facilitated diffusion_sentence_32

Just like prokaryotic cells, in eukaryotes, facilitated diffusion occurs in the nucleoplasm on chromatin filaments, accounted for by the switching dynamics of a protein when it is either bound to a chromatin thread or when freely diffusing in the nucleoplasm. Facilitated diffusion_sentence_33

In addition, given that the chromatin molecule is fragmented, its fractal properties need to be considered. Facilitated diffusion_sentence_34

After calculating the search time for a target protein, alternating between the 3-D and 1-D diffusion phases on the chromatin fractal structure, it was deduced that facilitated diffusion in eukaryotes precipitates the searching process and minimizes the searching time by increasing the DNA-protein affinity. Facilitated diffusion_sentence_35

For oxygen Facilitated diffusion_section_3

Oxygen binds with red blood cells in the blood stream. Facilitated diffusion_sentence_36

The oxygen affinity with hemoglobin on red blood cell surfaces enhances this bonding ability. Facilitated diffusion_sentence_37

In a system of facilitated diffusion of oxygen, there is a tight relationship between the ligand which is oxygen and the carrier which is either hemoglobin or myoglobin. Facilitated diffusion_sentence_38

This mechanism of facilitated diffusion of oxygen by hemoglobin or myoglobin was discovered and initiated by Wittenberg and Scholander. Facilitated diffusion_sentence_39

They carried out experiments to test for the steady-state of diffusion of oxygen at various pressures. Facilitated diffusion_sentence_40

Oxygen-facilitated diffusion occurs in a homogeneous environment where oxygen pressure can be relatively controlled. Facilitated diffusion_sentence_41

For oxygen diffusion to occur, there must be a full saturation pressure (more) on one side of the membrane and full reduced pressure (less) on the other side of the membrane i.e. one side of the membrane must be of higher concentration. Facilitated diffusion_sentence_42

During facilitated diffusion, hemoglobin increases the rate of constant diffusion of oxygen and facilitated diffusion occurs when oxyhemoglobin molecule is randomly displaced. Facilitated diffusion_sentence_43

For carbon monoxide Facilitated diffusion_section_4

Carbon monoxide has a facilitated diffusion process similar to that of oxygen. Facilitated diffusion_sentence_44

They both make use of the high affinity of hemoglobin and myoglobin for the gas. Facilitated diffusion_sentence_45

Carbon monoxide also combines with hemoglobin and myoglobin with the help of facilitated diffusion just as it is in oxygen but the rate at which they react differs from one another. Facilitated diffusion_sentence_46

Carbon monoxide has a dissociation velocity which is 100 times less than that of oxygen; its affinity for myoglobin is 40 times higher and 250 times higher for hemoglobin, compared to oxygen. Facilitated diffusion_sentence_47

For glucose Facilitated diffusion_section_5

Glucose is a six-carbon sugar that provides energy needed by cells. Facilitated diffusion_sentence_48

Since glucose is a large molecule, it is difficult to be transported across the membrane through simple diffusion. Facilitated diffusion_sentence_49

Hence, it diffuses across membranes through facilitated diffusion, down the concentration gradient. Facilitated diffusion_sentence_50

The carrier protein at the membrane binds to the glucose and alters its shape such that it can easily to be transported from one side of the membrane to the other. Facilitated diffusion_sentence_51

Movement of glucose into the cell could be rapid or slow depending on the number of membrane-spanning protein. Facilitated diffusion_sentence_52

It is transported against the concentration gradient by a dependent glucose symporter which provides a driving force to other glucose molecules in the cells. Facilitated diffusion_sentence_53

Facilitated diffusion helps in the release of accumulated glucose into the extracellular space adjacent to the blood capillary. Facilitated diffusion_sentence_54

See also Facilitated diffusion_section_6

Facilitated diffusion_unordered_list_1

Credits to the contents of this page go to the authors of the corresponding Wikipedia page: en.wikipedia.org/wiki/Facilitated diffusion.