Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Glycolysis and Gluconeogenesis edit
- ↑ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".
| glucose transporter, type 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | Glc_transpt_3IPR002945GLUT3Glucose transporter type 3brainGlut-3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | GeneCards: | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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. [1] GLUT3 facilitates the transport of glucose across the plasma membranes of mammalian cells. GLUT3 is most known for its specific expression in neurons and has originally been designated as the neuronal GLUT. GLUT3 has been studied in other cell types with specific glucose requirements, including sperm, preimplantation embryos, circulating white blood cells and carcinoma cell lines. [2]
GLUT3 was the third glucose transporter to be discovered, first cloned in 1988 from a fetal skeletal muscle cell line, using a GLUT1 cDNA probe and shown to share 64.4% identity with GLUT1. [1]
Although GLUT3 was found to be expressed in various tissues, it is most specifically expressed in neurons, found predominantly in axons and dendrites and also, but less prominently, in the cell body. [3] GLUT3 has at least a fivefold greater transport capacity than GLUT1 or GLUT4, as well as a higher glucose affinity than GLUT1, GLUT2 or GLUT4. This is significant as glucose levels surrounding the neurons are only 1–2 mM, compared to 5–6 mM in the serum. [2]
Glucose delivery and utilization in the mammalian brain is mediated primarily by a high molecular weight form of GLUT1 in the blood–brain barrier, GLUT3 in neuronal populations and a less glycosylated form of GLUT1 in the remainder of the parenchyma. GLUT3 is considered the main but not the exclusive neuronal glucose transporter, whereas other glucose transporters have also been observed in neurons. [3]
GLUT3 expression in neurons in the rat coincides with maturation and synaptic connectivity [4] and a positive correlation between protein levels of GLUT1, GLUT3 and regional cerebral glucose utilization was observed in mouse. [5]
The central role of GLUT3 in cerebral metabolism has been challenged by the astrocyte-neuron lactate shuttle (ANLS) hypothesis, [6] which proposes that astrocytes play the key role in the coupling of neuronal activity and cerebral glucose utilization. In this hypothesis, the astrocyte, which relies on GLUT1 for glucose transport, is the primary consumer of glucose in the brain, providing lactate as the primary energetic fuel for neurons. However, by modeling the kinetic characteristics and glucose concentrations in neurons and glia, it was concluded that the glucose capacity of neurons via GLUT3 far exceeds that of astrocytes via GLUT1. [7] Additionally, demonstrations of increase in GLUT3 expression associated with increased cerebral glucose utilization provides further confirmation of the central role of GLUT3. [5]
Expression of GLUT3 is also found in sperm, embryos, white blood cells and carcinoma cell lines.
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Glia, also called glial cells(gliocytes) or neuroglia, are non-neuronal cells in the central nervous system and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myelin in the peripheral nervous system, and provide support and protection for neurons. In the central nervous system, glial cells include oligodendrocytes, astrocytes, ependymal cells, and microglia, and in the peripheral nervous system they include Schwann cells and satellite cells.
In haemodynamics, the body must respond to physical activities, external temperature, and other factors by homeostatically adjusting its blood flow to deliver nutrients such as oxygen and glucose to stressed tissues and allow them to function. Haemodynamic response (HR) allows the rapid delivery of blood to active neuronal tissues. The brain consumes large amounts of energy but does not have a reservoir of stored energy substrates. Since higher processes in the brain occur almost constantly, cerebral blood flow is essential for the maintenance of neurons, astrocytes, and other cells of the brain. This coupling between neuronal activity and blood flow is also referred to as neurovascular coupling.
Astrocytes, also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, regulation of cerebral blood flow, and a role in the repair and scarring process of the brain and spinal cord following infection and traumatic injuries. The proportion of astrocytes in the brain is not well defined; depending on the counting technique used, studies have found that the astrocyte proportion varies by region and ranges from 20% to 40% of all glia. Another study reports that astrocytes are the most numerous cell type in the brain. Astrocytes are the major source of cholesterol in the central nervous system. Apolipoprotein E transports cholesterol from astrocytes to neurons and other glial cells, regulating cell signaling in the brain. Astrocytes in humans are more than twenty times larger than in rodent brains, and make contact with more than ten times the number of synapses.
Astrogliosis is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons from central nervous system (CNS) trauma, infection, ischemia, stroke, autoimmune responses or neurodegenerative disease. In healthy neural tissue, astrocytes play critical roles in energy provision, regulation of blood flow, homeostasis of extracellular fluid, homeostasis of ions and transmitters, regulation of synapse function and synaptic remodeling. Astrogliosis changes the molecular expression and morphology of astrocytes, in response to infection for example, in severe cases causing glial scar formation that may inhibit axon regeneration.
Glucose transporter 2 (GLUT2) also known as solute carrier family 2, member 2 (SLC2A2) is a transmembrane carrier protein that enables protein facilitated glucose movement across cell membranes. It is the principal transporter for transfer of glucose between liver and blood Unlike GLUT4, it does not rely on insulin for facilitated diffusion.
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 adipose tissues and striated muscle. The first evidence for this distinct glucose transport protein was provided by David James in 1988. The gene that encodes GLUT4 was cloned and mapped in 1989.
Glutamate transporters are a family OF neurotransmitter transporter proteins that move glutamate – the principal excitatory neurotransmitter – across a membrane. The family of glutamate transporters is composed of two primary subclasses: the excitatory amino acid transporter (EAAT) family and vesicular glutamate transporter (VGLUT) family. In the brain, EAATs remove glutamate from the synaptic cleft and extrasynaptic sites via glutamate reuptake into glial cells and neurons, while VGLUTs move glutamate from the cell cytoplasm into synaptic vesicles. Glutamate transporters also transport aspartate and are present in virtually all peripheral tissues, including the heart, liver, testes, and bone. They exhibit stereoselectivity for L-glutamate but transport both L-aspartate and D-aspartate.
Radial glial cells, or radial glial progenitor cells (RGPs), are bipolar-shaped progenitor cells that are responsible for producing all of the neurons in the cerebral cortex. RGPs also produce certain lineages of glia, including astrocytes and oligodendrocytes. Their cell bodies (somata) reside in the embryonic ventricular zone, which lies next to the developing ventricular system.
Glucose transporter 1, 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 across the plasma membranes of mammalian cells. This gene encodes a major glucose transporter in the mammalian blood-brain barrier. The encoded protein is found primarily in the cell membrane and on the cell surface, where it can also function as a receptor for human T-cell leukemia virus (HTLV) I and II. One good source of GLUT1 is erythrocyte membranes. GLUT1 accounts for 2 percent of the protein in the plasma membrane of erythrocytes. GLUT1, found in the plasma membrane of erythrocytes, is a classic example of a uniporter. After glucose is transported into the erythrocyte, it is rapidly phosphorylated, forming glucose-6-phosphate, which cannot leave the cell. Mutations in this gene can cause GLUT1 deficiency syndrome 1, GLUT1 deficiency syndrome 2, idiopathic generalized epilepsy 12, dystonia 9, and stomatin-deficient cryohydrocytosis.
The glia limitans, or the glial limiting membrane, is a thin barrier of astrocyte foot processes associated with the parenchymal basal lamina surrounding the brain and spinal cord. It is the outermost layer of neural tissue, and among its responsibilities is the prevention of the over-migration of neurons and neuroglia, the supporting cells of the nervous system, into the meninges. The glia limitans also plays an important role in regulating the movement of small molecules and cells into the brain tissue by working in concert with other components of the central nervous system (CNS) such as the blood–brain barrier (BBB).
Satellite glial cells, formerly called amphicytes, are glial cells that cover the surface of neuron cell bodies in ganglia of the peripheral nervous system. Thus, they are found in sensory, sympathetic, and parasympathetic ganglia. Both satellite glial cells (SGCs) and Schwann cells are derived from the neural crest of the embryo during development. SGCs have been found to play a variety of roles, including control over the microenvironment of sympathetic ganglia. They are thought to have a similar role to astrocytes in the central nervous system (CNS). They supply nutrients to the surrounding neurons and also have some structural function. Satellite cells also act as protective, cushioning cells. Additionally, they express a variety of receptors that allow for a range of interactions with neuroactive chemicals. Many of these receptors and other ion channels have recently been implicated in health issues including chronic pain and herpes simplex. There is much more to be learned about these cells, and research surrounding additional properties and roles of the SGCs is ongoing.
The subcommissural organ (SCO) is one of the circumventricular organs of the brain. It is a small glandular structure that is located in the posterior region of the third ventricle, near the entrance of the cerebral aqueduct.
The subgranular zone (SGZ) is a brain region in the hippocampus where adult neurogenesis occurs. The other major site of adult neurogenesis is the subventricular zone (SVZ) in the brain.
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 concentration in the intestinal lumen. GLUT5 is also expressed in skeletal muscle, testis, kidney, fat tissue (adipocytes), and brain.
Glial scar formation (gliosis) is a reactive cellular process involving astrogliosis that occurs after injury to the central nervous system. As with scarring in other organs and tissues, the glial scar is the body's mechanism to protect and begin the healing process in the nervous system.
Excitatory amino acid transporter 2 (EAAT2) also known as solute carrier family 1 member 2 (SLC1A2) and glutamate transporter 1 (GLT-1) is a protein that in humans is encoded by the SLC1A2 gene. Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.
Excitatory amino acid transporter 3 (EAAT3), is a protein that in humans is encoded by the SLC1A1 gene.
Endogenous regeneration in the brain is the ability of cells to engage in the repair and regeneration process. While the brain has a limited capacity for regeneration, endogenous neural stem cells, as well as numerous pro-regenerative molecules, can participate in replacing and repairing damaged or diseased neurons and glial cells. Another benefit that can be achieved by using endogenous regeneration could be avoiding an immune response from the host.
A neuronal lineage marker is an endogenous tag that is expressed in different cells along neurogenesis and differentiated cells such as neurons. It allows detection and identification of cells by using different techniques. A neuronal lineage marker can be either DNA, mRNA or RNA expressed in a cell of interest. It can also be a protein tag, as a partial protein, a protein or an epitope that discriminates between different cell types or different states of a common cell. An ideal marker is specific to a given cell type in normal conditions and/or during injury. Cell markers are very valuable tools for examining the function of cells in normal conditions as well as during disease. The discovery of various proteins specific to certain cells led to the production of cell-type-specific antibodies that have been used to identify cells.
Brain cells make up the functional tissue of the brain. The rest of the brain tissue is structural or connective called the stroma which includes blood vessels. The two main types of cells in the brain are neurons, also known as nerve cells, and glial cells also known as neuroglia.