Glucose transporters are a wide group of

membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

s that facilitate the transport of

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...

across the

plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

, a process known as

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 transmembra ...

. 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 A protein family is a group of evolutionarily related proteins. In many cases, a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. The term "protein family" should not be c ...

that is found in most mammalian cells. 14 GLUTS are encoded by

human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the n ...

. GLUT is a type of

uniporter A uniporter is a membrane transport protein that transports a single species of Substrate (biochemistry), substrate (Electric charge, charged or uncharged) across a cell membrane. It may use either facilitated diffusion and transport along a dif ...

transporter protein.

Synthesis of free glucose

Most non-

autotroph An autotroph or primary producer is an organism that produces complex organic compounds (such as carbohydrates, fats, and proteins) using carbon from simple substances such as carbon dioxide,Morris, J. et al. (2019). "Biology: How Life Works", ...

ic cells are unable to produce free

because they lack expression of

glucose-6-phosphatase The enzyme glucose 6-phosphatase (EC 3.1.3.9, G6Pase; systematic name D-glucose-6-phosphate phosphohydrolase) catalyzes the hydrolysis of glucose 6-phosphate, resulting in the creation of a phosphate group and free glucose: : D-glucose 6-phos ...

and, thus, are involved only in glucose uptake and

catabolism Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids, ...

. Usually produced only in

hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...

s, in fasting conditions, other tissues such as the intestines, muscles, brain, and kidneys are able to produce glucose following activation of

gluconeogenesis Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrat ...

Glucose transport in yeast

In ''

Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...

'' glucose transport takes place through

. The transport proteins are mainly from the Hxt family, but many other transporters have been identified.

Glucose transport in mammals

GLUTs are integral membrane proteins that contain 12 membrane-spanning

helices A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is formed as two intertwined helices, ...

with both the amino and carboxyl termini exposed on the

cytoplasmic In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. Th ...

side of the

. GLUT proteins transport

and related

hexose In chemistry, a hexose is a monosaccharide (simple sugar) with six carbon atoms. The chemical formula for all hexoses is C6H12O6, and their molecular weight is 180.156 g/mol. Hexoses exist in two forms, open-chain or cyclic, that easily convert ...

s according to a model of alternate conformation, which predicts that the transporter exposes a single substrate binding site toward either the outside or the inside of the cell. Binding of glucose to one site provokes 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 oth ...

associated with transport, and releases glucose to the other side of the membrane. The inner and outer glucose-binding sites are, it seems, located in transmembrane segments 9, 10, 11; also, the DLS motif located in the seventh transmembrane segment could be involved in the selection and affinity of transported substrate.

Types

Each glucose transporter

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

plays a specific role in glucose metabolism determined by its pattern of tissue expression, substrate specificity, transport kinetics, and regulated expression in different physiological conditions. To date, 14 members of the GLUT/SLC2 have been identified. On the basis of sequence similarities, the GLUT family has been divided into three subclasses.

Class I

Class I comprises the well-characterized glucose transporters GLUT1-GLUT4.

Classes II/III

Class II comprises: *

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 concen ...

(), a

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 galacto ...

transporter in

enterocytes Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase its s ...

* GLUT7 (), found in the small and large intestine, transporting glucose out of the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

* GLUT9 - () * GLUT11 () Class III comprises: * GLUT6 (), * GLUT8 (), *

GLUT10 Solute carrier family 2, facilitated glucose transporter member 10 is a protein that in humans is encoded by the ''SLC2A10'' gene. SLC2A10 is a member of the facilitative glucose transporter family, which plays a significant role in maintaining gl ...

(), * GLUT12 (), and * GLUT13, also H+/ ''myo''-inositol transporter HMIT (), primarily expressed in brain. Most members of classes II and III have been identified recently in homology searches of EST databases and the sequence information provided by the various

genome projects Genome projects are scientific endeavours that ultimately aim to determine the complete genome sequence of an organism (be it an animal, a plant, a fungus, a bacterium, an archaean, a protist or a virus) and to annotate protein-coding genes and ot ...

. The function of these new glucose transporter isoforms is still not clearly defined at present. Several of them (GLUT6, GLUT8) are made of motifs that help retain them intracellularly and therefore prevent glucose transport. Whether mechanisms exist to promote cell-surface translocation of these transporters is not ye known, but it has clearly been established that insulin does not promote GLUT6 and GLUT8 cell-surface translocation.

Discovery of sodium-glucose cotransport

In August 1960, in

Prague Prague ( ; cs, Praha ; german: Prag, ; la, Praga) is the capital and largest city in the Czech Republic, and the historical capital of Bohemia. On the Vltava river, Prague is home to about 1.3 million people. The city has a temperate ...

Robert K. Crane Robert Kellogg Crane (December 20, 1919 – October 31, 2010) was an American biochemist best known for his discovery of sodium–glucose cotransport. Biography Crane was born on December 20, 1919 in Palmyra, New Jersey, to Wilbur Fiske Crane, J ...

presented for the first time his discovery of the sodium-glucose

cotransport In Cellular Biology, cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane Second law of thermodynamics, from a region of lower concentration to a region of higher concentration—against the concentra ...

as the mechanism for intestinal glucose absorption. Crane's discovery of

was the first ever proposal of flux coupling in biology. Crane in 1961 was the first to formulate the cotransport concept to explain active transport. Specifically, he proposed that the accumulation of glucose in the intestinal epithelium across the

brush border A brush border (striated border or brush border membrane) is the microvilli-covered surface of simple cuboidal and simple columnar epithelium found in different parts of the body. Microvilli are approximately 100 nanometers in diameter and the ...

membrane was scoupled to downhill Na+ transport cross the brush border. This hypothesis was rapidly tested, refined, and extended oencompass the active transport of a diverse range of molecules and ions into virtually every cell type.

References

External links

* {{Sodium-glucose transporter modulators Transport proteins Integral membrane proteins Solute carrier family