Glucose transporter 3 also known as solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) is a protein

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 SLC2A3 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...

. GLUT3 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. GLUT3 is most known for its specific expression 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 and has originally been designated as the neuronal GLUT. GLUT3 has been studied in other cell types with specific glucose requirements, including sperm

Sperm

The term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...

, preimplantation embryo

Embryo

An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...

s, circulating white blood cell

White blood cell

White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...

s and carcinoma

Carcinoma

Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...

 cell lines.

Discovery

GLUT3 was the third glucose transporter to be discovered, first cloned in 1988 from a fetal skeletal muscle cell line, using a 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...

 cDNA probe and shown to share 64.4% identity with GLUT1 .

Function

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. GLUT3 has both a higher affinity for glucose and at least a fivefold greater transport capacity than GLUT1, GLUT2 and GLUT4, which is particularly significant for its role in neuronal glucose transport, where ambient glucose levels are fivefold lower than in serum.

Brain

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 remainer of the parenchyma. GLUT3 is considered the main but not the exclusive neuronal glucose tansporter, whereas other glucose transporters have also been observed in neurons.

GLUT3 expression in neurons in the rat coincides with maturation and synaptic conectivity and a positive correlation between protein levels of GLUT1, GLUT3 and regional cerebral glucose utilization was observed in mouse.

The central role of GLUT3 in cerebral metabolism has been challenged by the astrocyte-neuron lactate shuttle (ANLS) hypothesis, which proposes that astrocyte

Astrocyte

Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...

s 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. Additionally, demonstrations of increase in GLUT3 expression associated with increased cerebral glucose utilization provides further confirmation of the central role of GLUT3.

Other tissues

Expression of GLUT3 is also found in sperm, embryos, white blood cells and carcinoma cell lines.