Membrane transport protein

A membrane transport protein (or simply transporter) is a membrane protein[1] involved in the movement of ions, small
molecules, or macromolecules, such as another protein, across a biological membrane. Transport proteins are integral transmembrane
proteins; that is they exist permanently within and span the membrane across which they transport substances. The proteins may
assist in the movement of substances by facilitated diffusion or active transport. The two main types of proteins involved in such
transport are broadly categorized as either channels or carriers. The solute carriers and atypical SLCs[2] are secondary active or
facilitative transporters in humans.[3][4]

Contents
Difference between channels and carriers
Active transport
Facilitated diffusion
Reverse transport
Types
1: Channels/pores
2: Electrochemical potential-driven transporters
3: Primary active transporters
4: Group translocators
5: Electron carriers
Examples
Pathology
See also
References
External links

Difference between channels and carriers

A carrier is not open simultaneously to both the extracellular and intracellular environments. Either its inner gate is open, or outer
gate is open. In contrast, a channel can be open to both environments at the same time, allowing the molecules to diffuse without
interruption. Carriers have binding sites, but pores and channels do not.[5][6][7] When a channel is opened, millions of ions can pass
[8] Each
through the membrane per second, but only 100 to 1000 molecules typically pass through a carrier molecule in the same time.
carrier protein is designed to recognize only one substance or one group of very similar substances. Research has correlated defects in
specific carrier proteins with specific diseases.[9]

Active transport
Active transport is the movement of a substance across a membrane against its concentration gradient. This is usually to accumulate
high concentrations of molecules that a cell needs, such as glucose or amino acids. When the lipid bilayer is impermeable to the
molecule needing transport, active transport is also necessary. If the process uses chemical energy, such as adenosine triphosphate
(ATP), it is called primary active transport. Secondary active transport involves the use of an electrochemical gradient, and does not
use energy produced in the cell.[10] Unlike channel proteins which only transport substances through membranes passively, carrier
fusion, or via secondary active transport.[11] A carrier
proteins can transport ions and molecules either passively through facilitated dif
protein is required to move particles from areas of low concentration
to areas of high concentration. These carrier proteins have receptors
that bind to a specific molecule (substrate) needing transport. The
molecule or ion to be transported (the substrate) must first bind at a
binding site at the carrier molecule, with a certain binding affinity.
Following binding, and while the binding site is facing the same way,
the carrier will capture or occlude (take in and retain) the substrate
within its molecular structure and cause an internal translocation so The action of the sodium-potassium pumpis an
that the opening in the protein now faces the other side of the plasma example of primary active transport. The two
membrane.[12] The carrier protein substrate is released at that site, carrier proteins on the left are using ATP to move
sodium out of the cell against the concentration
according to its binding affinity there.
gradient. The proteins on the right are using
secondary active transport to move potassium into
Facilitated diffusion the cell.

Facilitated diffusion is the passage of molecules or ions across a

biological membrane through specific transport proteins and requires
no energy input. Facilitated diffusion is used especially in the case of
large polar molecules and charged ions; once such ions are dissolved
in water they cannot diffuse freely across cell membranes due to the
hydrophobic nature of the fatty acid tails of the phospholipids that
make up the bilayers. The type of carrier proteins used in facilitated
diffusion is slightly different from those used in active transport.
Facilitated diffusion in cell membrane, showing ion
They are still transmembrane carrier proteins, but these are gated
channels (left) and carrier proteins (three on the
transmembrane channels, meaning they do not internally translocate,
right).
nor require ATP to function. The substrate is taken in one side of the
gated carrier, and without using ATP the substrate is released into the
cell. They may be used as potential biomarkers

Reverse transport
Reverse transport, or transporter reversal, is a phenomenon in which the substrates of a membrane transport protein are moved in the
opposite direction to that of their typical movement by the transporter.[13][14][15][16][17] Transporter reversal typically occurs when a
membrane transport protein is phosphorylated by a particular protein kinase, which is an enzyme that adds a phosphate group to
proteins.[13][14]

Types
(Grouped by Transporter Classification databasecategories)

1: Channels/pores
α-helical protein channels such asvoltage-gated ion channel(VIC), ligand-gated ion channels(LGICs)
β-barrel porins such asaquaporin
channel-forming toxins, includingcolicins, diphtheria toxin, and others
Nonribosomally synthesized channels such asgramicidin
Holins; which function in export of enzymes that digest bacterial cell walls in an early step of cell lysis.
Facilitated diffusion occurs in and out of the cell membrane via channels/pores and carriers/porters.

Note:

Channels:
Channels are either in open state or closed state. When a channel is opened with a slight conformational switch, it is open to both
environment simultaneously (extracellular and intracellular)

Pores:
Pores are continuously open to these both environment, because they do not undergo
conformational changes. They are always open and active.

2: Electrochemical potential-driven transporters

This picture represents symport. The
2.A: Porters ( uniporters, symporters, antiporters), SLCs.[4]
yellow triangle shows the
Excitatory amino acid transporters(EAATs) concentration gradient for the yellow
circles while the green triangle shows
EAAT1
the concentration gradient for the
EAAT2
green circles and the purple rods are
EAAT3
the transport protein bundle. The
EAAT4
green circles are moving against
EAAT5
their concentration gradient through
Glucose transporter a transport protein which requires
Monoamine transporters, including: energy while the yellow circles move
Dopamine transporter (DAT) down their concentration gradient
which releases energy. The yellow
Norepinephrine transporter(NET)
circles produce more energy through
Serotonin transporter (SERT)
chemiosmosis than what is required
Vesicular monoamine transporters(VMAT)
to move the green circles so the
Adenine nucleotide translocator(ANT) movement is coupled and some
2.B: Nonribosomally synthesized porters, such as energy is cancelled out. One
The Nigericin (Nigericin) Family example is the lactose permease
which allows protons to go down its
The Ionomycin (Ionomycin) Family
concentration gradient into the cell
2.C: Ion-gradient-driven energizers
while also pumping lactose into the
cell.

3: Primary active transporters

3.A: P-P-bond-hydrolysis-driven transporters :

ATP-binding cassette transporter(ABC transporter), such asMDR,

CFTR
V-type ATPase ; ( "V" related to vacuolar ).
P-type ATPase ; ( "P" related to phosphorylation), such as :
The picture represents uniport. The
Na+/K+-ATPase
yellow triangle shows the
Plasma membrane Ca2+ ATPase
concentration gradient for the yellow
Proton pump
circles and the purple rods are the
F-type ATPase; ("F" related to factor), including: mitochondrialATP transport protein bundle. Since they
synthase, chloroplast ATP synthase1
move down their concentration
3.B: Decarboxylation-driven transporters gradient through a transport protein,
3.C: Methyltransfer-driven transporters they can release energy as a result
3.D: Oxidoreduction-driven transporters of chemiosmosis. One example is
3.E: Light absorption-driven transporters, such asrhodopsin GLUT1 which moves glucose down
its concentration gradient into the
cell.
4: Group translocators
The group translocators provide a special mechanism for the phosphorylation of
sugars as they are transported into bacteria (PEP group translocation)
5: Electron carriers
The transmembrane electron transfer carriers in the membrane include two-electron
carriers, such as the disulfide bond oxidoreductases (DsbB and DsbD in E. coli) as
well as one-electron carriers such as NADPH oxidase. Often these redox proteins are
not considered transport proteins.
This picture represents antiport. The
Examples yellow triangle shows the
concentration gradient for the yellow
Each carrier protein, even within the same cell membrane, is specific to one type or circles while the blue triangle shows
family of molecules. For example,GLUT1 is a named carrier protein found in almost the concentration gradient for the
blue circles and the purple rods are
all animal cell membranes that transports glucose across the bilayer. Other specific
the transport protein bundle. The
carrier proteins also help the body function in important ways. Cytochromes operate
blue circles are moving against their
in the electron transport chainas carrier proteins for electrons.[10] concentration gradient through a
transport protein which requires

Pathology energy while the yellow circles move

down their concentration gradient
A number of inherited diseases involve defects in carrier proteins in a particular which releases energy. The yellow
circles produce more energy through
substance or group of cells. Cysteinuria (cysteine in the urine and the bladder) is such
chemiosmosis than what is required
a disease involving defective cysteine carrier proteins in the kidney cell membranes.
to move the blue circles so the
This transport system normally removes cysteine from the fluid destined to become movement is coupled and some
urine and returns this essential amino acid to the blood. When this carrier energy is cancelled out. One
malfunctions, large quantities of cysteine remain in the urine, where it is relatively example is the sodium-proton
insoluble and tends to precipitate. This is one cause of urinary stones.[18] Some exchanger which allows protons to
go down their concentration gradient
vitamin carrier proteins have been shown to be overexpressed in patients with
into the cell while pumping sodium
malignant disease. For example, levels of riboflavin carrier protein (RCP) have been
out of the cell.
.[19]
shown to be significantly elevated in people with breast cancer

See also
Cotransport
Cotransporter
Ion channel
Permease
P-loop
Solute carrier family (classification)
TC number (classification)
Translocase
Vesicular transport protein

References
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2. Perland, Emelie; Bagchi, Sonchita; Klaesson, Axel; Fredriksson, Robert (2017-09-01). "Characteristics of 29 novel
atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and
neuronal co-expression"(http://rsob.royalsocietypublishing.org/content/7/9/170142) . Open Biology. 7 (9): 170142.
doi:10.1098/rsob.170142 (https://doi.org/10.1098%2Frsob.170142). ISSN 2046-2441 (https://www.worldcat.org/issn/
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(February 2004). "The ABCs of solute carriers: physiological, pathological and therapeutic implications of human
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4. Perland, Emelie; Fredriksson, Robert (March 2017). "Classification Systems of Secondary Activeransporters".
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External links
"Transport protein" at Dorland's Medical Dictionary

DDI Regulatory GuidanceRequest a guide to drug-drug interaction regulatory recommendations.

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