Na+-coupled monocarboxylate transporter 1 (electrogenic Na+ monocarboxylate cotransporter, Na+ iodide-related cotransporter, apical iodide transporter, solute carrier family 5 member 8, SLC5A8, AIT, SMCT, SMCT1)
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Function
- electrogenic Na+ & Cl- dependent Na+ coupled solute transporter
- transport of monocarboxylates
- short-chain fatty acids L-lactate, D-lactate, pyruvate, acetate, propionate, valerate, butyrate
- drugs nicotinate, benzoate, salicylate & 5-aminosalicylate
- ketone bodies beta-D-hydroxybutyrate, acetoacetate & alpha-ketoisocaproate
- Na+:substrate stoichiometry of between 4:1 & 2:1
- catalyzes passive carrier mediated diffusion of iodide
- mediates iodide transport from the thyrocyte into the colloid lumen through the apical membrane
- may be responsible for the absorption of D- lactate & monocarboxylate drugs from the intestinal tract
- acts as a tumor suppressor, suppressing colony formation in colon cancer, prostate cancer & glioma cell lines
- may play a critical role in the entry of L-lactate & ketone bodies into neurons by a process driven by an electrochemical Na+ gradient & hence contribute to the maintenance of the energy status & function of neurons
Inhibition:
- increase of iodide influx inhibited by addition of perchlorate (NaClO4), a competitive inhibitor of iodide uptake catalyzed by Na+ iodide symporter
- cotransport of monocarboxylates & nicotinate strongly inhibited by probenecid, nonsteroid anti-inflammatory drugs (ibuprofen, fenoprofen, ketprofen, naproxen) (Na+-dependent) or by prolonged exposure to external concentrations of monocarboxylates
- KM=1442 uM for beta-D-hydroxybutyate
- KM=2327 uM for beta-L-hydroxybutyate
- KM=1088 uM for D-lactate
- KM=184 uM for L-lactate
- KM=387 uM for pyruvate
- KM=213 uM for acetoacetate
- KM=209 uM for alpha-ketoisocaproate
Structure
Compartment
- membrane
- expressed at the apical membrane of normal tall thyrocytes & of colonic epithelial cells
Expression
- expressed in normal thyroid, localized at the apical pole of thyroid cells facing the colloid lumen
- expressed in normal colon
- present in normal kidney cortex, brain, prostate, gastric mucosa & breast tissue
- expression reactivated on treatment with a demethylating drug, 5-azacytidine
Pathology
- down-regulated in some primary cancers due to aberrant methylation
- significantly down-regulated in primary gliomas, gastric cancer, prostate cancer & breast cancer
- expression profoundly decreased in thyroid carcinomas
- absent in colon aberrant crypt foci & colon cancers