ENTs, including those in
parasiticprotozoa, 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]
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:
Molina-Arcas M, Trigueros-Motos L, Casado FJ, Pastor-Anglada M (Jun 2008). "Physiological and pharmacological roles of nucleoside transporter proteins". Nucleosides, Nucleotides & Nucleic Acids. 27 (6): 769–78.
doi:
10.1080/15257770802145819.
PMID18600539.
S2CID45851514.
References
^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.
doi:
10.1080/00498250801927427.
ISSN1366-5928.
PMID18668437.
S2CID86822179.
^
abBaldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD (Feb 2004). "The equilibrative nucleoside transporter family, SLC29". Pflügers Archiv. 447 (5): 735–43.
doi:
10.1007/s00424-003-1103-2.
PMID12838422.
S2CID8817821.
^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.
doi:
10.1007/s12094-015-1471-z.
ISSN1699-3055.
PMID26742940.
S2CID9451723.