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cellular biology Cell biology (also cellular biology or cytology) is a branch of biology that studies the Anatomy, structure, Physiology, function, and behavior of cell (biology), cells. All living organisms are made of cells. A cell is the basic unit of life th ...
, membrane transport refers to the collection of mechanisms that regulate the passage of
solutes In chemistry, a solution is defined by IUPAC as "A liquid or solid phase containing more than one substance, when for convenience one (or more) substance, which is called the solvent, is treated differently from the other substances, which are ...
such as
ions An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
and small
molecules A molecule is a group of two or more atoms that are held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemistry ...
through biological membranes, which are lipid bilayers that contain
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...
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. The movements of most solutes through the membrane are mediated by membrane transport proteins which are specialized to varying degrees in the transport of specific molecules. As the diversity and
physiology Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...
of the distinct cells is highly related to their capacities to attract different external elements, it is postulated that there is a group of specific transport proteins for each cell type and for every specific physiological stage. This differential expression is regulated through the differential transcription of the
genes In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
coding for these proteins and its translation, for instance, through genetic-molecular mechanisms, but also at the cell biology level: the production of these proteins can be activated by cellular signaling pathways, at the
biochemical Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, ...
level, or even by being situated in
cytoplasmic The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell and ...
vesicles. The cell membrane regulates the transport of materials entering and exiting the cell.


Background

Thermodynamically the flow of substances from one compartment to another can occur in the direction of a
concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...
or
electrochemical Electrochemistry is the branch of physical chemistry concerned with the relationship between electrical potential difference and identifiable chemical change. These reactions involve electrons moving via an electronically conducting phase (typi ...
gradient In vector calculus, the gradient of a scalar-valued differentiable function f of several variables is the vector field (or vector-valued function) \nabla f whose value at a point p gives the direction and the rate of fastest increase. The g ...
or against it. If the exchange of substances occurs in the direction of the gradient, that is, in the direction of decreasing potential, there is no requirement for an input of energy from outside the system; if, however, the transport is against the gradient, it will require the input of energy, metabolic energy in this case. For example, a classic chemical mechanism for separation that does not require the addition of external energy is dialysis. In this system a semipermeable membrane separates two solutions of different concentration of the same solute. If the membrane allows the passage of water but not the solute the water will move into the compartment with the greatest solute concentration in order to establish an
equilibrium Equilibrium may refer to: Film and television * ''Equilibrium'' (film), a 2002 science fiction film * '' The Story of Three Loves'', also known as ''Equilibrium'', a 1953 romantic anthology film * "Equilibrium" (''seaQuest 2032'') * ''Equilibr ...
in which the energy of the system is at a minimum. This takes place because the water moves from a high solvent concentration to a low one (in terms of the solute, the opposite occurs) and because the water is moving along a gradient there is no need for an external input of energy. The nature of biological membranes, especially that of its lipids, is
amphiphilic In chemistry, an amphiphile (), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'', nonpolar) properties. Such a compound is called amphiphilic or amphipathic. Amphiphilic c ...
, as they form bilayers that contain an internal
hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...
layer and an external
hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...
layer. This structure makes transport possible by simple or passive diffusion, which consists of the
diffusion Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
of substances through the membrane without expending metabolic energy and without the aid of transport proteins. If the transported substance has a net
electrical charge Electricity is the set of physical phenomena associated with the presence and motion of matter possessing an electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described by Maxwel ...
, it will move not only in response to a concentration gradient, but also to an
electrochemical gradient An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts: * The chemical gradient, or difference in Concentration, solute concentration across ...
due to the
membrane potential Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. It equals the interior potential minus the exterior potential. This is th ...
.
As few molecules are able to diffuse through a lipid membrane the majority of the transport processes involve transport proteins. These
transmembrane proteins A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently un ...
possess a large number of
alpha helices An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...
immersed in the lipid matrix. In bacteria these proteins are present in the beta lamina form. This structure probably involves a conduit through hydrophilic protein environments that cause a disruption in the highly hydrophobic medium formed by the lipids. These proteins can be involved in transport in a number of ways: they act as pumps driven by ATP, that is, by metabolic energy, or as channels of facilitated diffusion.


Thermodynamics

A physiological process can only take place if it complies with basic
thermodynamic Thermodynamics is a branch of physics that deals with heat, work, and temperature, and their relation to energy, entropy, and the physical properties of matter and radiation. The behavior of these quantities is governed by the four laws of th ...
principles. Membrane transport obeys physical laws that define its capabilities and therefore its biological utility.
A general principle of thermodynamics that governs the transfer of substances through membranes and other surfaces is that the exchange of free energy, Δ''G'', for the transport of a mole of a substance of concentration C1 in a compartment to another compartment where it is present at C2 is: :\Delta G = RT \log \frac When C2 is less than C1, Δ''G'' is negative, and the process is thermodynamically favorable. As the energy is transferred from one compartment to another, except where other factors intervene, an
equilibrium Equilibrium may refer to: Film and television * ''Equilibrium'' (film), a 2002 science fiction film * '' The Story of Three Loves'', also known as ''Equilibrium'', a 1953 romantic anthology film * "Equilibrium" (''seaQuest 2032'') * ''Equilibr ...
will be reached where C2=C1, and where Δ''G'' = 0. However, there are three circumstances under which this equilibrium will not be reached, circumstances which are vital for the ''in vivo'' functioning of biological membranes: * The macromolecules on one side of the membrane can bond preferentially to a certain component of the membrane or chemically modify it. In this way, although the concentration of the solute may actually be different on both sides of the membrane, the availability of the solute is reduced in one of the compartments to such an extent that, for practical purposes, no gradient exists to drive transport. * A membrane electrical potential can exist which can influence ion distribution. For example, for the transport of ions from the exterior to the interior, it is possible that: :\Delta G = RT \log \frac+ZF \Delta P Where F is Faraday's constant and Δ''P'' the membrane potential in
volts The volt (symbol: V) is the unit of electric potential, electric potential difference (voltage), and electromotive force in the International System of Units (SI). Definition One volt is defined as the electric potential between two point ...
. If Δ''P'' is negative and Z is positive, the contribution of the term ''ZFΔP'' to Δ''G'' will be negative, that is, it will favor the transport of cations from the interior of the cell. So, if the potential difference is maintained, the equilibrium state Δ''G'' = 0 will not correspond to an equimolar concentration of ions on both sides of the membrane. * If a process with a negative Δ''G'' is coupled to the transport process then the global Δ''G'' will be modified. This situation is common in active transport and is described thus: :\Delta G = RT \log \frac+\Delta G^b Where Δ''Gb'' corresponds to a favorable thermodynamic reaction, such as the hydrolysis of ATP, or the
co-transport 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 cellula ...
of a compound that is moved in the direction of its gradient.


Transport types


Passive diffusion and active diffusion

As mentioned above, passive diffusion is a spontaneous phenomenon that increases the
entropy Entropy is a scientific concept, most commonly associated with states of disorder, randomness, or uncertainty. The term and the concept are used in diverse fields, from classical thermodynamics, where it was first recognized, to the micros ...
of a system and decreases the free energy. The transport process is influenced by the characteristics of the transport substance and the nature of the bilayer. The diffusion velocity of a pure phospholipid membrane will depend on: * concentration gradient, * hydrophobicity, * size, * charge, if the molecule has a net charge. * temperature


Active and co-transport

In active transport a solute is moved against a concentration or electrochemical gradient; in doing so the transport proteins involved consume metabolic energy, usually ATP. In primary active transport the hydrolysis of the energy provider (e.g. ATP) takes place directly in order to transport the solute in question, for instance, when the transport proteins are
ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, ATP hydrolase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or ...
enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...
. Where the hydrolysis of the energy provider is indirect as is the case in
secondary active transport 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 ...
, use is made of the energy stored in an electrochemical gradient. For example, in
co-transport 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 cellula ...
use is made of the gradients of certain solutes to transport a target compound against its gradient, causing the dissipation of the solute gradient. It may appear that, in this example, there is no energy use, but hydrolysis of the energy provider is required to establish the gradient of the solute transported along with the target compound. The gradient of the
co-transport 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 cellula ...
ed solute will be generated through the use of certain types of proteins called biochemical pumps. The discovery of the existence of this type of transporter protein came from the study of the kinetics of cross-membrane molecule transport. For certain solutes it was noted that the transport velocity reached a plateau at a particular concentration above which there was no significant increase in uptake rate, indicating a log curve type response. This was interpreted as showing that transport was mediated by the formation of a substrate-transporter complex, which is conceptually the same as the enzyme-substrate complex of
enzyme kinetics Enzyme kinetics is the study of the rates of enzyme catalysis, enzyme-catalysed chemical reactions. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction are investigated. Studying an enzyme' ...
. Therefore, each transport protein has an affinity constant for a solute that is equal to the concentration of the solute when the transport velocity is half its maximum value. This is equivalent in the case of an enzyme to the Michaelis–Menten constant. Some important features of active transport in addition to its ability to intervene even against a gradient, its kinetics and the use of ATP, are its high selectivity and ease of selective pharmacological inhibition


Secondary active transporter proteins

Secondary active transporter proteins move two molecules at the same time: one against a gradient and the other with its gradient. They are distinguished according to the directionality of the two molecules: *
antiporter An antiporter (also called exchanger or counter-transporter) is an integral membrane protein that uses secondary active transport to move two or more molecules in opposite directions across a phospholipid membrane. It is a type of cotransporte ...
(also called exchanger or counter-transporter): move a molecule against its gradient and at the same time displaces one or more ions along its gradient. The molecules move in opposite directions. *
symporter A symporter is an integral membrane protein that is involved in the transport of two (or more) different molecules across the cell membrane in the same direction. The symporter works in the plasma membrane and molecules are transported across th ...
: move a molecule against its gradient while displacing one or more different ions along their gradient. The molecules move in the same direction. Both can be referred to as co-transporters.


Pumps

A pump is a protein that hydrolyses ATP to transport a particular solute through a membrane, and in doing so, generating an electrochemical gradient
membrane potential Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. It equals the interior potential minus the exterior potential. This is th ...
. This gradient is of interest as an indicator of the state of the cell through parameters such as the Nernst potential. In terms of membrane transport the gradient is of interest as it contributes to decreased system entropy in the
co-transport 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 cellula ...
of substances against their gradient. One of the most important pumps in animal cells is the sodium potassium pump, that operates through the following mechanism: # binding of three Na+ ions to their active sites on the pump which are bound to ATP. # ATP is hydrolyzed leading to phosphorylation of the cytoplasmic side of the pump, this induces a structure change in the protein. The phosphorylation is caused by the transfer of the terminal group of ATP to a residue of
aspartate Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. The L-isomer of aspartic acid is one of the 22 proteinogenic amino acids, i.e., the building blocks of protein ...
in the transport protein and the subsequent release of ADP. # the structure change in the pump exposes the Na+ to the exterior. The phosphorylated form of the pump has a low affinity for Na+ ions so they are released. # once the Na+ ions are liberated, the pump binds two molecules of K+ to their respective bonding sites on the extracellular face of the transport protein. This causes the dephosphorylation of the pump, reverting it to its previous conformational state, transporting the K+ ions into the cell. # The unphosphorylated form of the pump has a higher affinity for Na+ ions than K+ ions, so the two bound K+ ions are released into the
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
. ATP binds, and the process starts again.


Membrane selectivity

As the main characteristic of transport through a biological membrane is its selectivity and its subsequent behavior as a barrier for certain substances, the underlying physiology of the phenomenon has been studied extensively. Investigation into membrane selectivity have classically been divided into those relating to
electrolytes An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble salts, acids, and bases, dissolved in a polar solvent like water. Upon dissolving, t ...
and non-electrolytes.


Electrolyte selectivity

The ionic channels define an internal diameter that permits the passage of small ions that is related to various characteristics of the ions that could potentially be transported. As the size of the ion is related to its chemical species, it could be assumed ''a priori'' that a channel whose pore diameter was sufficient to allow the passage of one ion would also allow the transfer of others of smaller size, however, this does not occur in the majority of cases. There are two characteristics alongside size that are important in the determination of the selectivity of the membrane pores: the facility for
dehydration In physiology, dehydration is a lack of total body water that disrupts metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of water. Mild deh ...
and the interaction of the ion with the internal charges of the pore.
In order for an ion to pass through a pore it must dissociate itself from the water molecules that cover it in successive layers of
solvation Solvations describes the interaction of a solvent with dissolved molecules. Both ionized and uncharged molecules interact strongly with a solvent, and the strength and nature of this interaction influence many properties of the solute, includi ...
. The tendency to dehydrate, or the facility to do this, is related to the size of the ion: larger ions can do it more easily that the smaller ions, so that a pore with weak polar centres will preferentially allow passage of larger ions over the smaller ones. When the interior of the channel is composed of polar groups from the side chains of the component amino acids, the interaction of a dehydrated ion with these centres can be more important than the facility for dehydration in conferring the specificity of the channel. For example, a channel made up of histidines and arginines, with positively charged groups, will selectively repel ions of the same polarity, but will facilitate the passage of negatively charged ions. Also, in this case, the smallest ions will be able to interact more closely due to the spatial arrangement of the molecule (stericity), which greatly increases the charge-charge interactions and therefore exaggerates the effect.


Non-electrolyte selectivity

Non-electrolytes, substances that generally are hydrophobic and lipophilic, usually pass through the membrane by dissolution in the lipid bilayer, and therefore, by passive diffusion. For those non-electrolytes whose transport through the membrane is mediated by a transport protein the ability to diffuse is, generally, dependent on the partition coefficient K. Partially charged non-electrolytes, that are more or less polar, such as ethanol, methanol or urea, are able to pass through the membrane through aqueous channels immersed in the membrane. There is no effective regulation mechanism that limits this transport, which indicates an intrinsic vulnerability of the cells to the penetration of these molecules.


Creation of membrane transport proteins

There are several databases which attempt to construct phylogenetic trees detailing the creation of transporter proteins. One such resource is the Transporter Classification database


See also

* Cellular transport * Scramblases


References

{{Authority control Membrane transport