Equilibrative nucleoside transporter family

ENTs, including those in parasitic 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 cancers and viral diseases. By regulating the concentration of adenosine available to cell surface receptors, mammalian ENTs additionally influence physiological processes ranging from cardiovascular activity to neurotransmission.^[1]

In humans ENT are also known as SLC29, a group of plasmalemmal transport proteins which transport nucleoside substrates like adenosine into cells.^[2] There are four known human ENTs, designated ENT1, ENT2, ENT3, and ENT4.^[2][3] They are blocked by adenosine reuptake inhibitors like dipyridamole and dilazep, drugs used clinically for their vasodilatory properties.^[3][4]

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.^[5][6] hENT3 has a similar broad permeant selectivity for nucleosides and nucleobases and appears to function in intracellular membranes, including lysosomes. Gemcitabine, an anti-cancer drug, is transported by hENT1 and hENT3.^[7] hENT4 is uniquely selective for adenosine, and also transports a variety of organic cations.

The generalized transport reaction catalyzed by well characterized ENT family members is:

Nucleoside (out) → Nucleoside (in)

• Concentrative nucleoside transporter
• Nucleoside transporter

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