Uniporters, also known as solute carriers or facilitated transporters, are a type of

membrane transport protein 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 membrane proteins, integral transmembr ...

that passively transports solutes (small molecules, ions, or other substances) across a cell membrane. It uses

facilitated diffusion 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 transmembr ...

for the movement of solutes down their concentration gradient from an area of high concentration to an area of low concentration. Unlike

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 cellula ...

, 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. Uniporter carrier proteins work by binding to one

molecule A molecule is a group of two or more atoms that are held together by Force, 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 chemi ...

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...

at a time. Uniporter channels open in response to a stimulus and allow the free flow of specific molecules. There are several ways in which the opening of uniporter channels may be regulated: #

Voltage Voltage, also known as (electrical) potential difference, electric pressure, or electric tension, is the difference in electric potential between two points. In a Electrostatics, static electric field, it corresponds to the Work (electrical), ...

– Regulated by the difference in voltage across the membrane #

Stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phra ...

– Regulated by physical

pressure Pressure (symbol: ''p'' or ''P'') is the force applied perpendicular to the surface of an object per unit area over which that force is distributed. Gauge pressure (also spelled ''gage'' pressure)The preferred spelling varies by country and eve ...

on the transporter (as in the

cochlea The cochlea is the part of the inner ear involved in hearing. It is a spiral-shaped cavity in the bony labyrinth, in humans making 2.75 turns around its axis, the modiolus (cochlea), modiolus. A core component of the cochlea is the organ of Cort ...

of the

ear In vertebrates, an ear is the organ that enables hearing and (in mammals) body balance using the vestibular system. In humans, the ear is described as having three parts: the outer ear, the middle ear and the inner ear. The outer ear co ...

) #

Ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

– Regulated by the binding of a ligand to either the intracellular or extracellular side of the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

Uniporters are found in

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

, plasma membranes and

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s.The uniporter in the mitochondria is responsible for

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

uptake. The calcium channels are used for

cell signaling In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...

and triggering

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

. The calcium uniporter transports calcium across the inner mitochondrial membrane and is activated when calcium rises above a certain concentration. The amino acid transporters function in transporting neutral

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s for

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

production in brain cells.

Voltage-gated potassium channel Voltage-gated potassium channels (VGKCs) are potassium channel, transmembrane channels specific for potassium and Voltage-gated ion channel, sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a ...

s are also uniporters found in neurons and are essential for

action potential An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...

s. This channel is activated by a voltage gradient created by sodium-potassium pumps. When the membrane reaches a certain voltage, the channels open, which depolarizes the membrane, leading to an

being sent down the membrane.

Glucose transporter 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 transporte ...

s are found in the plasma membrane and play a role in transporting

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

. They help to bring glucose from the blood or extracellular space into cells usually to be utilized for metabolic processes in generating energy. Uniporters are essential for certain physiological processes in cells, such as nutrient uptake, waste removal, and maintenance of ionic balance.

Discovery

Scheme facilitated diffusion in cell membrane-en

Early research in the 19th and 20th centuries on

osmosis Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively permeable membrane, selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of ...

and

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 ...

provided the foundation for understanding the passive movement of molecules across cell membranes. In 1855, the physiologist

Adolf Fick Adolf Eugen Fick (3 September 1829 – 21 August 1901) was a German-born physician and physiologist. Early life and education Fick began his work in the formal study of mathematics and physics before realising an aptitude for medicine. He t ...

was the first to define osmosis and simple diffusion as the tendency for

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 ...

to move from a region of higher concentration to a lower concentration, also very well-known as

Fick's Laws of Diffusion Fick's laws of diffusion describe diffusion and were first posited by Adolf Fick in 1855 on the basis of largely experimental results. They can be used to solve for the diffusion coefficient, . Fick's first law can be used to derive his second ...

. Through the work of Charles Overton in the 1890s, the concept that the

biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell from the external environment or creates intracellular compartments by serving as a boundary between one part of th ...

is semipermeable became important to understanding the regulation of substances in and out of the cells. The discovery of

by Wittenberg and Scholander suggested that

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s in the cell membrane aid in the transport of molecules. In the 1960s - 1970s, studies on the transport of

and other nutrients highlighted the specificity and

selectivity Selectivity may refer to: Psychology and behaviour * Choice, making a selection among options * Discrimination, the ability to recognize differences * Socioemotional selectivity theory, in social psychology Engineering * Selectivity (radio), a ...

s. Technological advancements in biochemistry helped isolate and characterize these proteins from cell membranes. Genetic studies on

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

and

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...

identified genes responsible for encoding transporters. This led to the discovery of glucose transporters (GLUT proteins), with

GLUT1 Glucose transporter 1 (or GLUT1), also known as solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1), is a uniporter protein that in humans is encoded by the ''SLC2A1'' gene. GLUT1 facilitates the transport of glucose acro ...

being the first to be characterized. Identification of gene families encoding various transporters, such as solute carrier (SLC) families, also advanced knowledge on uniporters and its functions. Newer research is focusing on techniques using

recombinant DNA technology Molecular cloning is a set of experimental methods in molecular biology that are used to assemble recombinant DNA molecules and to direct their replication within host organisms. The use of the word ''cloning'' refers to the fact that the metho ...

electrophysiology Electrophysiology (from ee the Electron#Etymology, etymology of "electron" ; and ) is the branch of physiology that studies the electrical properties of biological cell (biology), cells and tissues. It involves measurements of voltage change ...

and advanced imaging to understand uniporter functions. These experiments are designed to clone and express transporter genes in host cells to further analyze the three-dimensional structure of uniporters, as well as directly observe the movement of ions through proteins in real-time. The discovery of

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s in uniporters has been linked to diseases such as

GLUT1 deficiency syndrome GLUT1 deficiency syndrome, also known as GLUT1-DS, De Vivo disease or Glucose transporter type 1 deficiency syndrome, is an autosomal dominant genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose a ...

cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...

Hartnup disease Hartnup disease (also known as " pellagra-like dermatosis" and "Hartnup disorder") is an autosomal recessive metabolic disorder affecting the absorption of nonpolar amino acids (particularly tryptophan that can be, in turn, converted into se ...

primary hyperoxaluria Primary hyperoxaluria is a rare condition (autosomal recessive) resulting in increased excretion of oxalate (up to 600 mg a day from normal 50 mg a day), with oxalate stones being common. Signs and symptoms Primary hyperoxaluria is an a ...

and

hypokalemic periodic paralysis Hypokalemic periodic paralysis (hypoKPP), also known as familial hypokalemic periodic paralysis (FHPP), is a rare, autosomal dominant channelopathy characterized by muscle weakness or paralysis when there is a fall in potassium levels in the bl ...

Types

Glucose transporter (GLUTs)

The glucose transporter (GLUTs) is a type of uniporter responsible for the

of glucose molecules across cell membranes.

Glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

is a vital energy source for most living cells, however, due to its large size, it cannot freely move through the cell membrane. The glucose transporter is specialized in transporting glucose specifically across the membrane. The GLUT proteins have several types of

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

, each distributed in different tissues and exhibiting different kinetic properties. Glucose-6-phosphatase system

GLUTs are

integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All transmembrane proteins can be classified as IMPs, but not all IMPs are transmembrane proteins. IMPs comp ...

s composed of 12 α-helix membrane spanning regions. The GLUT proteins are encoded by the SLC2 genes and categorized into three classes based on

amino acid sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...

similarity. Humans have been found to express fourteen GLUT proteins. Class I GLUTs include

, one of the most studied isoforms, and

GLUT2 Glucose transporter 2 (GLUT2) also known as solute carrier family 2 (facilitated glucose transporter), member 2 (SLC2A2) is a transmembrane carrier protein that enables protein facilitated glucose movement across cell membranes. It is the princi ...

. GLUT1 is found in various tissues like the

red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

, and blood-brain barrier and is responsible for basal

glucose uptake Glucose uptake is the process by which glucose molecules are transported from the bloodstream into cells through specialized membrane proteins called glucose transporters, primarily via facilitated diffusion or active transport mechanisms: Faci ...

. GLUT2 is predominantly found in the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

pancreas The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...

, and

small intestine The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...

s. It plays an important role in insulin secretion from pancreatic beta cells. Class II includes the

GLUT3 Glucose transporter 3 (or GLUT3), also known as solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) is a protein that in humans is encoded by the ''SLC2A3'' gene. GLUT3 facilitates the transport of glucose across the plas ...

and

GLUT4 Glucose transporter type 4 (GLUT4), also known as solute carrier family 2, facilitated glucose transporter member 4, is a protein encoded, in humans, by the ''SLC2A4'' gene. GLUT4 is the insulin-regulated glucose transporter found primarily in ad ...

. GLUT3, primarily found in the brain,

s and

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

, has a high

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for glucose in facilitating glucose uptake into neurons.

plays a role in insulin-regulated glucose uptake and is mainly found in insulin-sensitive tissues such as muscle and

adipose tissue Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...

. Class III includes

GLUT5 GLUT5 is a fructose transporter expressed on the apical border of enterocytes in the small intestine. GLUT5 allows for fructose to be transported from the intestinal lumen into the enterocyte by facilitated diffusion due to fructose's high conc ...

, found in the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

testes A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of androgens, primarily testosterone. The ...

, and

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

. Unlike the other GLUTs, GLUT5 specifically transports

fructose Fructose (), or fruit sugar, is a Ketose, ketonic monosaccharide, simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and gal ...

rather than glucose. Glucose transporters allow glucose molecules to move down their concentration gradient from areas of high glucose concentration to areas of low concentration. This process often involves bringing glucose from the

extracellular space Extracellular space refers to the part of a multicellular organism outside the cells, usually taken to be outside the plasma membranes, and occupied by fluid. This is distinguished from intracellular space, which is inside the cells. The composit ...

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

into the cell. The concentration gradient set up by glucose concentrations fuels the process without the need for ATP. When glucose binds to the glucose transporter, the protein channels change shape and undergo a conformational change to transport the glucose across the membrane. Once the glucose unbinds, the protein returns to its original shape. The glucose transporter is essential for carrying out physiological processes that require high energy demands in the brain, muscles, and kidneys by providing an adequate amount of energy substrate for

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

Diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

, an example of a condition that involves glucose metabolism, highlights the importance of the regulation of glucose uptake in disease management.

Mitochondrial uniporter (MCU)

The mitochondrial calcium uniporter (MCU) is a protein complex located in the inner mitochondrial matrix that functions to take up calcium ions (Ca2+) into the

matrix Matrix (: matrices or matrixes) or MATRIX may refer to: Science and mathematics * Matrix (mathematics), a rectangular array of numbers, symbols or expressions * Matrix (logic), part of a formula in prenex normal form * Matrix (biology), the m ...

from the

cytoplasm 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 a ...

. The transport of calcium ions is specifically used in cellular function for regulating energy production in the mitochondria, cytosolic

calcium signaling Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for a wide variety of cellular signaling pathways. Once Ca2+ enters the cytosol of the ...

, and

cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as di ...

. The uniporter becomes activated when cytoplasmic levels of calcium rise above 1 uM. The MCU complex comprises 4 parts: the port-forming subunits, regulatory subunits MICU1 and MICU2, and an auxiliary subunit, EMRE. These subunits work together to regulate the uptake of calcium in the mitochondria. Specifically, the EMRE subunit functions for the transport of calcium, and the MICU subunit functions in tightly regulating the activity of MCU to prevent the overload of calcium concentrations in the cytoplasm. Calcium is fundamental for signaling pathways in cells, as well as for cell death pathways. The function of the mitochondrial uniporter is critical for maintaining cellular

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

. The MICU1 and MICU2 subunits are a

heterodimer In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...

connected by a

disulfide bridge In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inorg ...

. When there are high levels of cytoplasmic calcium, the MICU1-MICU2 heterodimer undergoes a

conformational change In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors. A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or othe ...

. The heterodimer subunits have cooperative activation, which means binding to one MICU subunit in the heterodimer induces a conformational change on the other MICU subunits. The uptake of calcium is balanced by the

sodium-calcium exchanger The sodium-calcium exchanger (often denoted Na+/Ca2+ exchanger, exchange protein, or NCX) is an antiporter membrane protein that removes calcium from cells. It uses the energy that is stored in the electrochemical gradient of sodium (Na+) by ...

Large neutral amino acid transporter (LAT1)

The L-type amino acid transporter (LAT1) is a uniporter that mediates the transport of neutral amino acids like L-tryptophan,

leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α-Car ...

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic ...

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the p ...

alanine Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group sid ...

, etc. LAT1 favors the transport of amino acids with large branched or aromatic side chains. The amino acid transporter functions to move essential amino acids into the

intestinal epithelium The intestinal epithelium is the single cell layer that forms the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelium its main functions are absorptio ...

, and blood-brain barrier for cellular processes such as metabolism and cell signaling. The transporter is of particular significance in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

as it provides the necessary amino acids for protein synthesis and neurotransmitter production in brain cells.

Aromatic amino acid An aromatic amino acid is an amino acid that includes an aromaticity, aromatic ring. Among the 20 standard amino acids, histidine, phenylalanine, tryptophan, tyrosine, are classified as aromatic. Properties and function Optical properties Ar ...

s like

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the chemical formula, formula . It can be viewed as a benzyl group substituent, substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of ...

and

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

are precursors for neurotransmitters like

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

, and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

. LAT1 is a membrane protein of the SLC7 family of transporters and works in conjunction with the SLC3 family member 4F2hc to form a

heterodimeric In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...

complex known as the 4F2hc complex. The heterodimer consists of a light chain and a heavy chain

covalently bonded A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atoms ...

by a

disulfide bond In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inor ...

. The light chain is the one that carries out transport, while the heavy chain is needed to stabilize the dimer. There is some controversy over whether LAT1 is an uniporter or an

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 ...

. The transporter has uniporter characteristics of transporting amino acids into cells in a unidirectional manner down the concentration gradient. However, recently it has been found that the transporter has antiporter characteristics of exchanging neutral amino acids for abundant intracellular amino acids. Over-expression of LAT1 has been found in human

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

and is associated with playing a role in cancer metabolism.

Equilibrative nucleoside transporters (ENTs)

The nucleoside transporters, or equilibrative nucleoside transporters, are uniporters that transport

nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotid ...

nucleobase Nucleotide bases (also nucleobases, nitrogenous bases) are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nuc ...

s, and

therapeutic drugs Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between ...

across the cell membrane. Nucleosides serve as building blocks for nucleic acid synthesis and are key components for energy metabolism in creating ATP/ GTP. They also act as ligands for

purinergic receptors Purinergic receptors, also known as purinoceptors, are a family of plasma membrane molecules that are found in almost all mammalian tissues. Within the field of purinergic signalling, these receptors have been implicated in learning and memory, ...

such as

adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside build ...

and

inosine Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring (also known as a ribofuranose) via a β-N9-glycosidic bond. It was discovered in 1965 in analysis of RNA transferase. Inosine is commonly found in tRNAs and is ...

. ENTs allow the transport of nucleosides down their concentration gradient. They also have the ability to deliver nucleoside analogs to intracellular targets for the treatment of

tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

and viral infections. ENTs are part of the Major Facilitator Superfamily (MFS) and are suggested to transport nucleosides using a clamp-and-switch model. In this model, the substrate first binds to the transporter, which leads to a conformational change that forms an occluded state (clamp). Then, the transporter switches to face the other side of the membrane and releases the bound substrate (switching). ENTs have been found in

protozoa Protozoa (: protozoan or protozoon; alternative plural: protozoans) are a polyphyletic group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic debris. Historically ...

and mammals. In humans, they have been discovered as ENT3 (hENT1-3) and

ENT4 The plasma membrane monoamine transporter (PMAT) is a low-affinity monoamine transporter protein which in humans is encoded by the ''SLC29A4'' gene. It is known alternatively as the human equilibrative nucleoside transporter-4 (hENT4). It was disc ...

(hENT4) transporters. ENTs are expressed across all tissue types, but certain ENT proteins have been found to be more abundant in specific tissues. hENT1 is found mostly in the

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...

ovary The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/ oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are end ...

stomach The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...

and

s. hENT2 is expressed mostly in neurological tissues and small parts of the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

, placenta,

urinary bladder The bladder () is a hollow organ in humans and other vertebrates that stores urine from the Kidney (vertebrates), kidneys. In placental mammals, urine enters the bladder via the ureters and exits via the urethra during urination. In humans, the ...

heart muscle Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of ...

and

gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow Organ (anatomy), organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath t ...

. hENT3 is expressed highly in the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...

lateral ventricle The lateral ventricles are the two largest ventricular system, ventricles of the brain and contain cerebrospinal fluid. Each cerebral hemisphere contains a lateral ventricle, known as the left or right lateral ventricle, respectively. Each later ...

and

. hENT4 is more commonly known as the plasma membrane monoamine transporter (PMAT), as it facilitates the movement of organic

cations 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 biogenic

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

s across the membrane.

Mechanism

Uniporters work to transport molecules or ions by

passive transport 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 ...

across a cell membrane down its concentration gradient. Upon binding and recognition of a specific substrate molecule on one side of the uniporter membrane, a

is triggered in the transporter protein. This causes the transporter protein to change its three-dimensional shape, which ensures the substrate molecule is captured within the transporter proteins structure. The conformational change leads to the translocation of the substrate across the membrane onto the other side. On the other side of the membrane, the uniporter undergoes another conformational change in the release of the substrate molecule. The uniporter returns to its original conformation to bind another molecule for transport. Unlike

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 ...

s and

s, uniporters transport one molecule/ion in a single direction based on the concentration gradient. The entire process depends on the substrate's concentration difference across the membrane to be the driving force for the transport by uniporters. Cellular energy in the form of ATP is not required for this process.

Physiological processes

Uniporters play an essential role in carrying out various cellular functions. Each uniporter is specialized to facilitate the transport of a specific molecule or ion across the cell membrane. Examples of a few of the physiological roles uniporters aid in include: # Nutrient Uptake: Uniporters facilitate the transport of essential

nutrient A nutrient is a substance used by an organism to survive, grow and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...

s into the cell. Glucose transporters (GLUTs) are uniporters that uptake glucose for

energy production Energy development is the field of activities focused on obtaining sources of energy from natural resources. These activities include the production of renewable, nuclear, and fossil fuel derived sources of energy, and for the recovery and re ...

. # Ion homeostasis: Uniporters facilitate in maintaining the balance of ions (i.e., , , ) within cells # Metabolism: Uniporters are involved in the transport of essential ions,

s and molecules required for the metabolic pathway, Protein biosynthesis, protein synthesis and energy production # Cell signaling: Calcium uniporters help regulate intercellular calcium levels essential for signal transduction # Waste removal: Uniporters aid in removing metabolic waste products and toxins from cells # Acid–base homeostasis, pH regulation: Transport of ions by uniporters also helps to maintain the overall acid-base balance within cells

Mutations

Mutations in genes encoding uniporters lead to dysfunctional transporter proteins being formed. This loss of function in uniporters causes disruption in cellular function which leads to various diseases and disorders.

References

{{Membrane transport Integral membrane proteins Transport phenomena

Discovery

Types

Glucose transporter (GLUTs)

Mitochondrial uniporter (MCU)

Large neutral amino acid transporter (LAT1)

Equilibrative nucleoside transporters (ENTs)

Mechanism

Physiological processes

Mutations

See also

References