OAT1 is believed oat bread no wheat have twelve transmembrane domains. The membrane is represented in light brown.

PBB GE SLC22A6 216599 x at fs. PBB GE SLC22A6 210343 s at fs. OAT1 functions as organic anion exchanger. To prevent the loss of endogenous dicarboxylates, OAT1-positive cells also express a sodium-dicarboxylate cotransporter called NaDC3 that transports dicarboxylates back into the OAT1-positive cell.

Sodium is required to drive this process. In the absence of a sodium gradient across the cell membrane, the NaDC3 cotransporter ceases to function, intra-cellular dicarboxylates are depleted, and the OAT1 transporter also grinds to a halt. Alterations in the expression and function of OAT1 play important roles in intra- and inter-individual variability of the therapeutic efficacy and the toxicity of many drugs. As a result, the activity of OAT1 must be under tight regulation so as to carry out their normal functions.

Nucleoside analogs are a class of antiviral drugs that work by inhibiting viral nucleic acid synthesis. Stavudine also causes severe mitochondrial DNA depletion. Combining zidovudine with stavudine does not increase the mitochondrial toxicity compared to stavudine alone. Lamivudine has reverse chirality compared to didanosine, stavudine, zidovudine, and natural nucleosides. Mitochondrial DNA polymerase may not recognize it as a substrate.

Lamivudine is not toxic to mitochondria in vivo. Cloning of a human renal p-aminohippurate transporter, hROAT1″. Cloning of the human kidney PAH transporter: narrow substrate specificity and regulation by protein kinase C”. Molecular physiology of renal organic anion transporters”. National Center for Biotechnology Information, U. Stellmer F, Keyser B, Burckhardt BC, et al. 3-Hydroxyglutaric acid is transported via the sodium-dependent dicarboxylate transporter NaDC3″.

Posttranslational Regulation of Organic Anion Transporters by Ubiquitination: Known and Novel”. Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1″. Fanconi syndrome and lactic acidosis associated with stavudine and lamivudine therapy”. Abacavir-induced reversible Fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immunodeficiency syndrome”. Fanconi syndrome associated with cidofovir therapy”.

Editorial comment: tenofovir nephrotoxicity–the disconnect between clinical trials and real-world practice”. Vidal F, Domingo JC, Guallar J, et al. In vitro cytotoxicity and mitochondrial toxicity of tenofovir alone and in combination with other antiretrovirals in human renal proximal tubule cells”. Viengchareun S, Caron M, Auclair M, et al. Mitochondrial toxicity of indinavir, stavudine and zidovudine involves multiple cellular targets in white and brown adipocytes”. Honkoop P, de Man RA, Scholte HR, Zondervan PE, Van Den Berg JW, Rademakers LH, et al. Effect of lamivudine on morphology and function of mitochondria in patients with chronic hepatitis B.