Members of the Equilibrative Nucleoside Transporter (ENT) Family
TC# 2.A.57
are transport proteins that are specific to

nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleoti ...

s and

nucleobase Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic b ...

s, and are part of the

major facilitator superfamily The major facilitator superfamily (MFS) is a superfamily of membrane transport proteins that facilitate movement of small solutes across cell membranes in response to chemiosmotic gradients. Function The major facilitator superfamily (MFS) are ...

. They generally possess at least 6, typically 10, transmembrane segments (TMSs) and are 300-600 amino acyl residues in length.

Function

ENTs, including those in

parasitic Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson ha ...

protozoa, function in nucleoside and nucleobase uptake for salvage pathways of nucleotide synthesis and, in humans, are also responsible for the cellular uptake of nucleoside analogues used in the treatment of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

s and

viral disease A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Structural Characteristics Basic structural characteristics, ...

s. By regulating the concentration of adenosine available to cell surface receptors, mammalian ENTs additionally influence physiological processes ranging from cardiovascular activity to

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...

Human ENTs

In humans ENT are also known as SLC29, a group of

plasmalemmal 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 (th ...

transport protein A transport protein (variously referred to as a transmembrane pump, transporter, escort protein, acid transport protein, cation transport protein, or anion transport protein) is a protein that serves the function of moving other materials within ...

s which transport

substrates like adenosine into

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

s. There are four known human ENTs, designated ENT1, ENT2, ENT3, and ENT4. They are blocked by

adenosine reuptake inhibitor An adenosine reuptake inhibitor (AdoRI) is a type of drug which acts as a reuptake inhibitor for the purine nucleoside and neurotransmitter adenosine by blocking the action of one or more of the equilibrative nucleoside transporters (ENTs). This ...

s like

dipyridamole Dipyridamole (trademarked as Persantine and others) is a nucleoside transport inhibitor and a PDE3 inhibitor medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a ...

and

dilazep Dilazep is a vasodilator that acts as an adenosine reuptake inhibitor. It is used for the treatment of cardiopathy and renal disorders. Synthesis The reaction of bis-(3-hydroxypropyl)-ethylene diamine (1) with 1-Bromo-3-chloropropane (2) gives ...

, drugs used clinically for their

vasodilatory Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...

properties. The best-characterized members of the human Ent family, hENT1 and hENT2, possess similar broad permeant selectivities for purine and pyrimidine nucleosides, but hENT2 also efficiently transports nucleobases. hENT3 has a similar broad permeant selectivity for nucleosides and nucleobases and appears to function in intracellular membranes, including lysosomes.

Gemcitabine Gemcitabine, with brand names including Gemzar, is a chemotherapy medication. It treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer. It is administered by ...

, an anti-cancer drug, is transported by hENT1 and hENT3. hENT4 is uniquely selective for adenosine, and also transports a variety of organic cations.

Transport Reaction

The generalized transport reaction catalyzed by well characterized ENT family members is: : Nucleoside (out) → Nucleoside (in)

References

{{CCBYSASource, sourcepath=PASTE TCDB URL HERE, sourcearticle=PASTE TCDB ARTICLE TITLE HERE, revision=699838558 Protein families Membrane proteins Transmembrane proteins Transmembrane transporters Transport proteins Integral membrane proteins

Function

Human ENTs

Transport Reaction

See also

Further reading

References