Equilibrative nucleoside transporter family explained

Members of the Equilibrative Nucleoside Transporter (ENT) Family (TC# 2.A.57) are transport proteins that are specific to nucleosides and nucleobases, and are part of the major facilitator superfamily. 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 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]

Human ENTs

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.

Transport reaction

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

Nucleoside (out) → Nucleoside (in)

See also

• Concentrative nucleoside transporter
• Nucleoside transporter

Further reading

• Molina-Arcas M, Trigueros-Motos L, Casado FJ, Pastor-Anglada M . Physiological and pharmacological roles of nucleoside transporter proteins . Nucleosides, Nucleotides & Nucleic Acids . 27 . 6 . 769–78 . Jun 2008 . 18600539 . 10.1080/15257770802145819 . 45851514 .

Notes and References

1. Young. J. D.. Yao. S. Y. M.. Sun. L.. Cass. C. E.. Baldwin. S. A.. 2008-07-01. Human equilibrative nucleoside transporter (ENT) family of nucleoside and nucleobase transporter proteins. Xenobiotica. 38. 7–8. 995–1021. 10.1080/00498250801927427. 1366-5928. 18668437. 86822179.
2. Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD . The equilibrative nucleoside transporter family, SLC29 . Pflügers Archiv . 447 . 5 . 735–43 . Feb 2004 . 12838422 . 10.1007/s00424-003-1103-2 . 8817821 .
3. Molina-Arcas M, Casado FJ, Pastor-Anglada M . Nucleoside transporter proteins . Current Vascular Pharmacology . 7 . 4 . 426–34 . Oct 2009 . 19485885 . 10.2174/157016109789043892 . https://archive.today/20130113054147/http://www.bentham-direct.org/pages/content.php?CVP/2009/00000007/00000004/002AD.SGM . dead . 2013-01-13 . 10.1.1.319.2647 .
4. Noji T, Karasawa A, Kusaka H . Adenosine uptake inhibitors . European Journal of Pharmacology . 495 . 1 . 1–16 . Jul 2004 . 15219815 . 10.1016/j.ejphar.2004.05.003 .
5. Engel. Karen. Zhou. Mingyan. Wang. Joanne. 2004-11-26. Identification and characterization of a novel monoamine transporter in the human brain. The Journal of Biological Chemistry. 279. 48. 50042–50049. 10.1074/jbc.M407913200. 0021-9258. 15448143. free.
6. Griffiths. Mark. 15 Dec 1997. Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta.. Biochemical Journal. 328. 3. 10.1042/bj3280739. 9396714. 1218980. 739–43.
7. Orlandi. A.. Calegari. M. A.. Martini. M.. Cocomazzi. A.. Bagalà. C.. Indellicati. G.. Zurlo. V.. Basso. M.. Cassano. A.. 2016-10-01. Gemcitabine versus FOLFIRINOX in patients with advanced pancreatic adenocarcinoma hENT1-positive: everything was not too bad back when everything seemed worse. Clinical & Translational Oncology. 18. 10. 988–995. 10.1007/s12094-015-1471-z. 1699-3055. 26742940. 9451723.