OAT1 is a transmembrane protein that is expressed in the brain, the placenta, the eyes, smooth muscles, and the basolateral membrane of proximal tubular cells of the kidneys.

Along with OAT3, OAT1 mediates the uptake of a wide range of relatively small and hydrophilic organic anions from plasma into the cytoplasm of the proximal tubular cells of the kidneys.

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.

[11] The regulation of OAT transport activity in response to various stimuli can occur at several levels such as transcription, translation, and posttranslational modification.

Posttranslational regulation is of particular interest, because it usually happens within a very short period of time (minutes to hours) when the body has to deal with rapidly changing amounts of substances as a consequence of variable intake of drugs, fluids, or meals as well as metabolic activity.

[11] Post-translational modification is a process where new functional group(s) are conjugated to the amino acid side chains in a target protein through reversible or irreversible biochemical reactions.

The nucleoside analogs acyclovir (ACV), zidovudine (AZT), didanosine (ddI), zalcitabine (ddC), lamivudine (3TC), stavudine (d4T), trifluridine,[12] cidofovir, adefovir,[13] and tenofovir (TDF) [14] are substrates of the OAT1 transporter.

Clinical features of tenofovir-induced Fanconi syndrome include glycosuria in the setting of normal serum glucose levels, phosphate wasting with hypophosphatemia, proteinuria (usually mild), acidosis, and hypokalemia, with or without acute renal failure.

[18] Since nucleoside analogs can build up in OAT1-positive cells and can inhibit mitochondrial replication, these drugs may lead to the depletion of mitochondria inside renal proximal tubules.

[19] In vitro the antiviral drugs didanosine and zidovudine are more potent inhibitors of mitochondrial DNA synthesis than tenofovir (ddI > AZT > TDF).