Glucose transporter
Encyclopedia
Glucose transporters are a wide group of membrane protein
s that facilitate the transport of glucose
over a plasma membrane. 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 cell
s.
cells are unable to produce free glucose
because they lack expression of glucose-6-phosphatase and, thus, are involved only in glucose uptake
and catabolism
. Usually only produced in hepatocyte
s, in fasting conditions other tissues such as the intestines, muscles, brain and kidneys are able to produce glucose following activation of gluconeogenesis
.
glucose transport takes place through facilitated diffusion
. The transport proteins are mainly from the Hxt family, but many other transporters have been identified.
and related hexose
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 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 QLS
motif located in the seventh transmembrane segment could be involved in the selection and affinity of transported substrate.
Class III comprises:
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.
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 yet known, but it has clearly been established that insulin does not promote GLUT6 and GLUT8 cell-surface translocation.
presented for the first time his discovery of the sodium-glucose cotransport
as the mechanism for intestinal glucose absorption. Crane
's discovery of cotransport
was the first ever proposal of flux coupling in biology.
Membrane protein
A membrane protein is a protein molecule that is attached to, or associated with the membrane of a cell or an organelle. More than half of all proteins interact with membranes.-Function:...
s that facilitate the transport of glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
over a plasma membrane. Because glucose is a vital source of energy for all life these transporters are present in all phyla
Phylum
In biology, a phylum The term was coined by Georges Cuvier from Greek φῦλον phylon, "race, stock," related to φυλή phyle, "tribe, clan." is a taxonomic rank below kingdom and above class. "Phylum" is equivalent to the botanical term division....
. The GLUT or SLC2A family are a protein family that is found in most mammalian cell
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s.
Synthesis of free glucose
Most non-autotrophicAutotroph
An autotroph, or producer, is an organism that produces complex organic compounds from simple inorganic molecules using energy from light or inorganic chemical reactions . They are the producers in a food chain, such as plants on land or algae in water...
cells are unable to produce free glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
because they lack expression of glucose-6-phosphatase and, thus, are involved only in glucose uptake
Uptake
Uptake may refer to:*Diffusion , the acceptance or adoption of a new product or idea.*Absorption, especially of food or nutrient by an organism. **Mineral uptake, by plants...
and catabolism
Catabolism
Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...
. Usually only produced in hepatocyte
Hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...
s, in fasting conditions other tissues such as the intestines, muscles, brain and kidneys are able to produce glucose following activation of gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
.
Glucose transport in yeast
In Saccharomyces cerevisiaeSaccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
glucose transport takes place through facilitated diffusion
Facilitated diffusion
..Facilitated diffusion is a process of passive transport, facilitated by integral proteins. Facilitated diffusion is the spontaneous passage of molecules or ions across a biological membrane passing through specific transmembrane integral proteins...
. The transport proteins are mainly from the Hxt family, but many other transporters have been identified.
| Name | Properties | Notes >- | Snf3 Snf3 Snf3 is a protein which regulates glucose uptake in yeast. It senses glucose in the environment with high affinity.-Introduction:Glucose sensing and signaling in budding yeast is similar to the mammalian system in many ways. However there are also significant differences. Mammalian cells regulate... |
>- | >- | Km: 100 mM, 129 - 107 mM | >- | Km = 1.5 - 10 mM | >- | Vm = 18.5, Kd = 0.078, Km = 28.6/34.2 - 60 mM | >- | Vm = 12.0, Kd = 0.049, Km = 6.2 | >- | Km = 10 mM | >- | Vm = 11.4, Kd = 0.029, Km = 0.9/14, 1.5 mM | >- | Vm = 11.7, Kd = 0.039, Km = 1.3, 1.9, 1.5 mM | >- | >- | >- | >- | Vm = 17.5, Kd = 0.043, Km = 1.5, 1.6 | high galactose affinity |
Glucose transport in Mammals
GLUTs are integral membrane proteins that contain 12 membrane-spanning helices with both the amino and carboxyl termini exposed on the cytoplasmic side of the plasma membrane. GLUT proteins transport glucoseGlucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
and related hexose
Hexose
In organic chemistry, a hexose is a monosaccharide with six carbon atoms, having the chemical formula C6H12O6. Hexoses are classified by functional group, with aldohexoses having an aldehyde at position 1, and ketohexoses having a ketone at position 2....
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 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 QLS
Dynamic light scattering
thumb|right|350px|Hypothetical Dynamic light scattering of two samples: Larger particles on the top and smaller particle on the bottomDynamic light scattering is a technique in physics that can be used to determine the size distribution profile of small particles in suspension or polymers...
motif located in the seventh transmembrane segment could be involved in the selection and affinity of transported substrate.
Types
Each glucose transporter isoform 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, 13 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.| Name | Distribution | Notes >- | GLUT1 GLUT1 Glucose transporter 1 , also known as solute carrier family 2, facilitated glucose transporter member 1 is a protein that in humans is encoded by the SLC2A1 gene... |
Is widely distributed in fetal Fetus A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The... tissues. In the adult, it is expressed at highest levels in erythrocytes and also in the endothelial cells of barrier tissues such as the blood-brain barrier Blood-brain barrier The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion... . However, it is responsible for the low-level of basal glucose uptake required to sustain respiration in all cells. |
>- | Is a bidirectional transporter, allowing glucose to flow in 2 directions. Is expressed by renal tubular cells, small intestinal epithelial cells, liver Liver The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion... cells and pancreatic β cells. Bidirectionality is required in liver cells to uptake glucose for glycolysis, and release of glucose during gluconeogenesis. In pancreatic β-cells, free flowing glucose is required so that the intracellular environment of these cells can accurately gauge the serum glucose levels. All three monosaccharides (glucose Glucose Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate... , galactose Galactose Galactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose.... and fructose Fructose Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847... ) are transported from the intestinal mucosal cell into the portal circulation by GLUT2 |
>- | Expressed mostly in neuron Neuron A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous... s (where it is believed to be the main glucose transporter isoform), and in the placenta Placenta The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and... . |
>- | Found in adipose tissue Adipose tissue In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts... s and striated muscle Striated muscle Striated muscle tissue is a form of fibers that are combined into parallel fibers. More specifically, it can refer to:* Cardiac muscle .* Skeletal muscle* Branchiomeric muscles... (skeletal muscle Skeletal muscle Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle... and cardiac muscle Cardiac muscle Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle... ). |
Is the insulin Insulin Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle.... -regulated glucose transporter. Responsible for insulin-regulated glucose storage. |
Classes II/III
Class II comprises:- GLUT5 , a fructoseFructoseFructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...
transporter - GLUT7 - SLC2A7SLC2A7Solute carrier family 2, facilitated glucose transporter member 7 also known as glucose transporter 7 is a protein that in humans is encoded by the SLC2A7 gene....
- , transporting glucose out of the endoplasmic reticulumEndoplasmic reticulumThe endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae... - GLUT9 - SLC2A9SLC2A9Solute carrier family 2, facilitated glucose transporter member 9 is a protein that in humans is encoded by the SLC2A9 gene.SLC2A9 has also recently been found to transport uric acid, and genetic variants of the transporter have been linked to increased risk of development of both hyperuricemia and...
- - GLUT11
Class III comprises:
- GLUT6 ,
- GLUT8 ,
- GLUT10 ,
- GLUT12 , and
- the H+/myoinositol transporter HMIT .
Most members of classes II and III have been identified recently in homology searches of EST
Expressed sequence tag
An expressed sequence tag or EST is a short sub-sequence of a cDNA sequence. They may be used to identify gene transcripts, and are instrumental in gene discovery and gene sequence determination. The identification of ESTs has proceeded rapidly, with approximately 65.9 million ESTs now available in...
databases and the sequence information provided by the various genome projects.
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 yet 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, Robert K. CraneRobert K. Crane
Robert Kellogg Crane is an American biochemist best known for his discovery of sodium-glucose cotransport.-Biography:...
presented for the first time his discovery of the sodium-glucose cotransport
Co-transport
Co-transport, also known as coupled transport or secondary active transport, refers to the simultaneous or sequential passive transfer of molecules or ions across biological membranes in a fixed ratio...
as the mechanism for intestinal glucose absorption. Crane
Robert K. Crane
Robert Kellogg Crane is an American biochemist best known for his discovery of sodium-glucose cotransport.-Biography:...
's discovery of cotransport
Co-transport
Co-transport, also known as coupled transport or secondary active transport, refers to the simultaneous or sequential passive transfer of molecules or ions across biological membranes in a fixed ratio...
was the first ever proposal of flux coupling in biology.