A membrane transport protein is a membrane protein involved in the movement of ions, small molecules, and 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, active transport, osmosis, or reverse diffusion. The two main types of proteins involved in such transport are broadly categorized as either channels or carriers (a.k.a. transporters, or permeases). Examples of channel/carrier proteins include the GLUT 1 uniporter, sodium channels, and potassium channels. The solute carriers and atypical SLCs [1] are secondary active or facilitative transporters in humans. [2] [3] Collectively membrane transporters and channels are known as the transportome. [4] Transportomes govern cellular influx and efflux of not only ions and nutrients but drugs as well.
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 through the membrane per second, but only 100 to 1000 molecules typically pass through a carrier molecule in the same time. [8] Each 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 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. If the process uses chemical energy, such as adenosine triphosphate (ATP), it is called primary active transport. Membrane transport proteins that are driven directly by the hydrolysis of ATP are referred to as ATPase pumps. [10] These types of pumps directly the exergonic hydrolysis of ATP to the unfavorable movement of molecules against their concentration gradient. Examples of ATPase pumps include P-type ATPase's, V-type ATPases, F-type ATPases, and ABC binding casettes.[ citation needed ]
Secondary active transport involves the use of an electrochemical gradient, and does not use energy produced in the cell. [11] Secondary active transport commonly uses types of carrier proteins, typically symporters and antiporters. Symporter proteins couple the transport of one molecule down its concentration gradient to the transport of another molecule against its concentration gradient, and both molecules diffuse in the same direction. Antiporter proteins transport one molecule down its concentration gradient to transport another molecule against its concentration gradient, but the molecules diffuse in opposite directions. As symporters and antiporters are involved in coupling the transport of two molecules, they are commonly referred to as cotransporters. Unlike channel proteins which only transport substances through membranes passively, carrier proteins can transport ions and molecules either passively through facilitated diffusion, or via secondary active transport. [12] A carrier 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 that the opening in the protein now faces the other side of the plasma membrane. [13] The carrier protein substrate is released at that site, according to its binding affinity there.[ citation needed ]
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. They are still transmembrane carrier proteins, but these are gated transmembrane channels, meaning they do not internally translocate, 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. Facilitated diffusion does not require the use of ATP as facilitated diffusion, like simple diffusion, transports molecules or ions along their concentration gradient. [14]
Osmosis is the passive diffusion of water across a cell membrane from an area of high concentration to an area of low concentration. Since Osmosis is a passive process, like facilitated diffusion and simple diffusion, it does not require the use of ATP. Osmosis is important in regulating the balance of water and salt within cells, thus it plays a critical role in maintaining homeostasis. [15] Aquaporins are integral membrane proteins that allow for the rapid passage of water and glycerol through membranes. The aquaporin monomers consist of six transmembrane alpha-helix domains and these monomers can assemble to form the aquaporin proteins. As four of these monomers come together to form the aquaporin protein, it is known as a homotetramer, meaning it is made up of four identical subunits. [16] [17] All aquaporins are tetrameric membrane integral proteins, and the water passes through each individual monomer channel rather than between all of the four channels. Since aquaporins are transmembrane channels for the diffusion of water, the channels that make up the aquaporin are typically lined with hydrophilic side chains to allow water to pass through.
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. [18] [19] [20] [21] [22] 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. [18] [19]
(Grouped by Transporter Classification database categories)
Facilitated diffusion occurs in and out of the cell membrane via channels/pores and carriers/porters.
Note:
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 are continuously open to these both environment, because they do not undergo conformational changes. They are always open and active.
Also named carrier proteins or secondary carriers.
The group translocators provide a special mechanism for the phosphorylation of sugars as they are transported into bacteria (PEP group translocation)
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.
Every carrier protein, especially within the same cell membrane, is specific to one type or family of molecules. GLUT1 is a named carrier protein found in almost all animal cell membranes that transports glucose across the bilayer. This protein is a uniporter, meaning it transports glucose along its concentration in a singular direction. It is an integral membrane protein carrier with a hydrophilic interior, which allows it to bind to glucose. As GLUT 1 is a type of carrier protein, it will undergo a conformational change to allow glucose to enter the other side of the plasma membrane. [23] GLUT 1 is commonly found in the red blood cell membranes of mammals. [24]
While there are many examples of channels within the human body, two notable ones are sodium and potassium channels. Potassium channels are typically involved in the transport of potassium ions across the cell membrane to the outside of the cell, which helps maintain the negative membrane potential of cells. As there are more potassium channels than sodium channels, more potassium flows out of the cell than sodium into a cell, thus why the membrane potential is negative. Sodium channels are typically involved in the transport of sodium ions across the cell membrane into the cell. These channels are commonly associated with excitable neurons, as an influx of sodium can trigger depolarization, which in turn propagates an action potential. [25] As these proteins are types of channel proteins, they do not undergo a change of conformation after binding their respective substrates.
Other specific carrier proteins also help the body function in important ways. Cytochromes operate in the electron transport chain as carrier proteins for electrons. [11]
A number of inherited diseases involve defects in carrier proteins in a particular substance or group of cells. Cysteinuria (cysteine in the urine and the bladder) is such a disease involving defective cysteine carrier proteins in the kidney cell membranes. This transport system normally removes cysteine from the fluid destined to become urine and returns this essential amino acid to the blood. When this carrier malfunctions, large quantities of cysteine remain in the urine, where it is relatively insoluble and tends to precipitate. This is one cause of urinary stones. [26] Some vitamin carrier proteins have been shown to be overexpressed in patients with malignant disease. For example, levels of riboflavin carrier protein (RCP) have been shown to be significantly elevated in people with breast cancer. [27]
Facilitated diffusion is the process of spontaneous passive transport of molecules or ions across a biological membrane via specific transmembrane integral proteins. 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 according to the principles of diffusion.
In cellular biology, active transport is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellular energy to achieve this movement. There are two types of active transport: primary active transport that uses adenosine triphosphate (ATP), and secondary active transport that uses an electrochemical gradient. This process is in contrast to passive transport, which allows molecules or ions to move down their concentration gradient, from an area of high concentration to an area of low concentration, without energy.
ATPases (EC 3.6.1.3, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or the inverse reaction. This dephosphorylation reaction releases energy, which the enzyme (in most cases) harnesses to drive other chemical reactions that would not otherwise occur. This process is widely used in all known forms of life.
The sodium–potassium pump is an enzyme found in the membrane of all animal cells. It performs several functions in cell physiology.
Passive transport is a type of membrane transport that does not require energy to move substances across cell membranes. Instead of using cellular energy, like active transport, passive transport relies on the second law of thermodynamics to drive the movement of substances across cell membranes. Fundamentally, substances follow Fick's first law, and move from an area of high concentration to an area of low concentration because this movement increases the entropy of the overall system. The rate of passive transport depends on the permeability of the cell membrane, which, in turn, depends on the organization and characteristics of the membrane lipids and proteins. The four main kinds of passive transport are simple diffusion, facilitated diffusion, filtration, and/or osmosis.
Mediated transport refers to transport mediated by a membrane transport protein. Substances in the human body may be hydrophobic, electrophilic, contain a positively or negatively charge, or have another property. As such there are times when those substances may not be able to pass over the cell membrane using protein-independent movement. The cell membrane is imbedded with many membrane transport proteins that allow such molecules to travel in and out of the cell. There are three types of mediated transporters: uniport, symport, and antiport. Things that can be transported are nutrients, ions, glucose, etc, all depending on the needs of the cell. One example of a uniport mediated transport protein is GLUT1. GLUT1 is a transmembrane protein, which means it spans the entire width of the cell membrane, connecting the extracellular and intracellular region. It is a uniport system because it specifically transports glucose in only one direction, down its concentration gradient across the cell membrane.
In cellular biology, membrane transport refers to the collection of mechanisms that regulate the passage of solutes such as ions and small molecules through biological membranes, which are lipid bilayers that contain proteins embedded in them. The regulation of passage through the membrane is due to selective membrane permeability – a characteristic of biological membranes which allows them to separate substances of distinct chemical nature. In other words, they can be permeable to certain substances but not to others.
Uniporters, also known as solute carriers or facilitated transporters, are a type of membrane transport protein that passively transports solutes across a cell membrane. It uses facilitated diffusion for the movement of solutes down their concentration gradient from an area of high concentration to an area of low concentration. Unlike active transport, it does not require energy in the form of ATP to function. Uniporters are specialized to carry one specific ion or molecule and can be categorized as either channels or carriers. Facilitated diffusion may occur through three mechanisms: uniport, symport, or antiport. The difference between each mechanism depends on the direction of transport, in which uniport is the only transport not coupled to the transport of another solute.
An antiporter is an integral membrane protein involved in secondary active transport. It is a type of cotransporter, which means that uses the movement of one In the case of an antiporter, two or more different molecules or ions are moved across a phospholipid membrane, such as the plasma membrane, in opposite directions, one into the cell and one out of the cell. This is in contrast to symporters, which are another type of cotransporter that moves two or more ions in the same direction.
Cotransporters are a subcategory of membrane transport proteins (transporters) that couple the favorable movement of one molecule with its concentration gradient and unfavorable movement of another molecule against its concentration gradient. They enable coupled or cotransport and include antiporters and symporters. In general, cotransporters consist of two out of the three classes of integral membrane proteins known as transporters that move molecules and ions across biomembranes. Uniporters are also transporters but move only one type of molecule down its concentration gradient and are not classified as cotransporters.
Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporters are present in all phyla. The GLUT or SLC2A family are a protein family that is found in most mammalian cells. 14 GLUTS are encoded by the human genome. GLUT is a type of uniporter transporter protein.
In biology, an ion transporter is a transmembrane protein that moves ions across a biological membrane to accomplish many different biological functions, including cellular communication, maintaining homeostasis, energy production, etc. There are different types of transporters including pumps, uniporters, antiporters, and symporters. Active transporters or ion pumps are transporters that convert energy from various sources—including adenosine triphosphate (ATP), sunlight, and other redox reactions—to potential energy by pumping an ion up its concentration gradient. This potential energy could then be used by secondary transporters, including ion carriers and ion channels, to drive vital cellular processes, such as ATP synthesis.
Method of glucose uptake differs throughout tissues depending on two factors; the metabolic needs of the tissue and availability of glucose. The two ways in which glucose uptake can take place are facilitated diffusion and secondary active transport. Active transport is the movement of ions or molecules going against the concentration gradient.
The galactose permease or GalP found in Escherichia coli is an integral membrane protein involved in the transport of monosaccharides, primarily hexoses, for utilization by E. coli in glycolysis and other metabolic and catabolic pathways (3,4). It is a member of the Major Facilitator Super Family (MFS) and is homologue of the human GLUT1 transporter (4). Below you will find descriptions of the structure, specificity, effects on homeostasis, expression, and regulation of GalP along with examples of several of its homologues.
Sodium-dependent glucose cotransporters are a family of glucose transporter found in the intestinal mucosa (enterocytes) of the small intestine (SGLT1) and the proximal tubule of the nephron. They contribute to renal glucose reabsorption. In the kidneys, 100% of the filtered glucose in the glomerulus has to be reabsorbed along the nephron. If the plasma glucose concentration is too high (hyperglycemia), glucose passes into the urine (glucosuria) because SGLT are saturated with the filtered glucose.
A symporter is an integral membrane protein that is involved in the transport of two different molecules across the cell membrane in the same direction. The symporter works in the plasma membrane and molecules are transported across the cell membrane at the same time, and is, therefore, a type of cotransporter. The transporter is called a symporter, because the molecules will travel in the same direction in relation to each other. This is in contrast to the antiport transporter. Typically, the ion(s) will move down the electrochemical gradient, allowing the other molecule(s) to move against the concentration gradient. The movement of the ion(s) across the membrane is facilitated diffusion, and is coupled with the active transport of the molecule(s). In symport, two molecule move in a 'similar direction' at the 'same time'. For example, the movement of glucose along with sodium ions. It exploits the uphill movement of other molecules from low to high concentration, which is against the electrochemical gradient for the transport of solute molecules downhill from higher to lower concentration.
Translocase is a general term for a protein that assists in moving another molecule, usually across a cell membrane. These enzymes catalyze the movement of ions or molecules across membranes or their separation within membranes. The reaction is designated as a transfer from “side 1” to “side 2” because the designations “in” and “out”, which had previously been used, can be ambiguous. Translocases are the most common secretion system in Gram positive bacteria.
Transcellular transport involves the transportation of solutes by a cell through a cell. Transcellular transport can occur in three different ways active transport, passive transport, and transcytosis.
Bacterial Leucine Transporter (LeuT) is a bundled twelve alpha helix protein which belongs to the family of transporters that shuttle amino acids in and out of bacterial cells. Specialized in small hydrophobic amino acids such as leucine and alanine, this transporter is powered by the gradient of sodium ions that is normally maintained by healthy cells across their membranes. LeuT acts as a symporter, which means that it links the passage of a sodium ion across the cell membrane with the transport of the amino acid in the same direction. It was first crystallized to understand the inner molecular mechanisms of antidepressant's work since it has a close resemblance with the human neurotransmitter transporters that these drugs block, thus inhibiting the reuptake of chemical messengers across the cell membrane of nerve axons and glial cells.
Wilfred D. Stein is a writer and biophysicist who has applied mathematical principles to medical, biologic, and oncologic problems.
Anderle, P., Barbacioru,C., Bussey, K., Dai, Z., Huang, Y., Papp, A., Reinhold, W., Sadee, W., Shankavaram, U., & Weinstein, J. (2004). Membrane Transporters and Channels: Role of the Transportome in Cancer Chemosensitivity and Chemoresistance. Cancer Research, 54, 4294-4301.