GLUT1
Encyclopedia
Glucose transporter 1 also known as solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) is a protein
that in humans is encoded by the SLC2A1 gene
. GLUT1 facilitates
the transport of glucose
across the plasma membranes
of mammalian cells.
, where the glucose concentration is maintained at about 5mM. Glucose enters the erythrocyte by facilitated diffusion
via a specific glucose transporter, at a rate about 50,000 times greater than uncatalyzed transmembrane diffusion. The glucose transporter of erythrocytes (called GLUT1 to distinguish it from related glucose transporters in other tissues) is a type III integral protein with 12 hydrophobic segments, each of which is believed to form a membrane-spanning helix
. The detailed structure of GLUT1 is not known yet, but one plausible model suggests that the side-by-side assembly of several helices produces a transmembrane channel
lined with hydrophilic residues that can hydrogen-bond with glucose as it moves through the channel.
GLUT1 is responsible for the low-level of basal glucose uptake required to sustain respiration in all cells. Expression levels of GLUT1 in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels.
GLUT1 is also a major receptor for uptake of Vitamin C
as well as glucose
, especially in non vitamin C producing mammals as part of an adaptation to compensate by participating in a Vitamin C recycling process. In mammals that do produce Vitamin C, GLUT4
is often expressed instead of GLUT1.
.
, which is a rare autosomal dominant disorder. This disease is characterized by a low cerebrospinal fluid
glucose concentration (hypoglycorrhachia), a type of neuroglycopenia
, which results from impaired glucose transport across the blood-brain barrier.
GLUT1 is also a receptor used by the HTLV
virus to gain entry into target cells.
with GIPC1
.
GLUT1 has two significant types in brain 45k and 55k. GLUT1 45k is present on astroglia of neurons and GLUT1 55k is present on capillaries in brain and is responsible for glucose transport across blood brain barrier and its deficiency causes low level of glucose in CSF(less than 60mg/dl) which may manifest as convulsion in deficient individuals.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the SLC2A1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. GLUT1 facilitates
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 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...
across the plasma membranes
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
of mammalian cells.
Function
Energy-yielding metabolism in erythrocytes depends on a constant supply of glucose from the blood plasmaBlood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
, where the glucose concentration is maintained at about 5mM. Glucose enters the erythrocyte by 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...
via a specific glucose transporter, at a rate about 50,000 times greater than uncatalyzed transmembrane diffusion. The glucose transporter of erythrocytes (called GLUT1 to distinguish it from related glucose transporters in other tissues) is a type III integral protein with 12 hydrophobic segments, each of which is believed to form a membrane-spanning helix
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
. The detailed structure of GLUT1 is not known yet, but one plausible model suggests that the side-by-side assembly of several helices produces a transmembrane channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
lined with hydrophilic residues that can hydrogen-bond with glucose as it moves through the channel.
GLUT1 is responsible for the low-level of basal glucose uptake required to sustain respiration in all cells. Expression levels of GLUT1 in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels.
GLUT1 is also a major receptor for uptake of Vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
as well as 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...
, especially in non vitamin C producing mammals as part of an adaptation to compensate by participating in a Vitamin C recycling process. In mammals that do produce Vitamin C, GLUT4
GLUT4
Glucose transporter type 4, also known as GLUT4, is a protein that in humans is encoded by the GLUT4 gene. GLUT4 is the insulin-regulated glucose transporter found in adipose tissues and striated muscle that is responsible for insulin-regulated glucose translocation into the cell...
is often expressed instead of GLUT1.
Tissue distribution
It is widely distributed in fetal 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 barrierBlood-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...
.
Structure
GLUT1 behaves as a Michaelis-Menten enzyme and contains 12 membrane-spanning alpha helices, each containing 20 amino acid residues. A helical wheel analysis shows that the membrane spanning alpha helices are amphipathic, with one side being polar and the other side hydrophobic. Six of these membrane spanning helices are believed to bind together in the membrane to create a polar channel in the center through which glucose can traverse, with the hydrophobic regions on the outside of the channel adjacent to the fatty acid tails of the membrane.Clinical significance
Mutations in the GLUT1 gene are responsible for GLUT1 deficiency or De Vivo diseaseDe Vivo disease
De Vivo disease is an autosomal dominant developmental disorder associated with a deficiency of GLUT1 also known as Glucose transporter type 1 deficiency syndrome -Presentation:...
, which is a rare autosomal dominant disorder. This disease is characterized by a low cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
glucose concentration (hypoglycorrhachia), a type of neuroglycopenia
Neuroglycopenia
Neuroglycopenia is a medical term that refers to a shortage of glucose in the brain, usually due to hypoglycemia. Glycopenia affects the function of neurons, and alters brain function and behavior...
, which results from impaired glucose transport across the blood-brain barrier.
GLUT1 is also a receptor used by the HTLV
Human T-lymphotropic virus
Human T-cell Lymphotropic Virus Type 1 , also called the Adult T-cell lymphoma virus type 1, a virus that has been seriously implicated in several kinds of diseases including HTLV-I-associated myelopathy, Strongyloides stercoralis hyper-infection, and a virus cancer link for leukemia...
virus to gain entry into target cells.
Interactions
GLUT1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with GIPC1
GIPC1
GIPC PDZ domain containing family, member 1 is a protein that in humans is encoded by the GIPC1 gene.-Interactions:GIPC1 has been shown to interact with Beta-1 adrenergic receptor, ITGA5, ITGA6, TPBG, RGS19, TYRP1, GLUT1, Actinin, alpha 1, KIF1B, LRP2, Luteinizing hormone/choriogonadotropin...
.
GLUT1 has two significant types in brain 45k and 55k. GLUT1 45k is present on astroglia of neurons and GLUT1 55k is present on capillaries in brain and is responsible for glucose transport across blood brain barrier and its deficiency causes low level of glucose in CSF(less than 60mg/dl) which may manifest as convulsion in deficient individuals.