Transactions of the Karelian Research Centre of the Russian Academy of Sciences (Dec 2017)

ORGANIC ANION TRANSPORTERS. MOLECULAR DIVERSITY, STRUCTURE, CONTRIBUTION TO THE FUNCTIONING OF THE XENOBIOTIC BIOTRANSFORMATION SYSTEM IN ANIMALS (A REWIEW)

  • Lev Smirnov,
  • Irina Sukhovskaya,
  • Ekaterina Borvinskaya

DOI
https://doi.org/10.17076/eb622
Journal volume & issue
no. 12
pp. 28 – 42

Abstract

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The organic anion transporter (OAT) subfamily, which constitutes roughly a half of the SLC22 transporter family and shares many structural characteristics with other MFS proteins, has received a great deal of attention because of its role in handling of common drugs, toxins, and nutrients (vitamins, flavonoids). OAT coding genes are expressed in many tissues, including kidney, liver, olfactory mucosa, brain, retina, and placenta. We currently know of 10 OATs, 7 in humans and 8 in rodents. OATs can be regarded as a part of the evolutionarily conservative system that protects higher organisms against potentially toxic compounds encountered in the environment. OATs polypeptide chain consists of 536–556 amino acid residues. Like in other members of the MFS superfamily, a characteristic trait of the molecule secondary structure is 12 transmembrane helices and intracellular localization of the N- and C-termini of the molecule, a large extracellular loop between domains 1 and 2, and a large intracellular loop connecting domains 6 and 7. Nuclear receptors, such as Hnf4α and Hnf1α, appear to regulate the expression of OATs in conjunction with phase I and phase II drug metabolizing enzymes. According to the “Remote Sensing and Signaling Hypothesis,” OATs can be involved in remote interorgan communication by regulating the levels of signaling molecules and key metabolites in tissues and body fluids. OATs can also play a part in interorganismal communication by transporting small molecules via the intestine, placental barrier, into breast milk, as well as volatile odorants via urine.

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