The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter.
Level 5 - mechanism / opinion, no new human data
In vitro functional expression and electrophysiological characterization in Xenopus oocytes (mechanistic bench research).
PubMed 15090606 · doi:10.1113/jphysiol.2004.063859
What was done
Human SLC5A8 protein was expressed in Xenopus laevis oocytes to characterize its transport mechanism, ion dependence, substrate affinity, and pharmacological inhibition using electrophysiological measurements.
What was found
SLC5A8 functioned as an electrogenic Na+-dependent monocarboxylate cotransporter (designated SMCT) with a 3:1 Na+:monocarboxylate stoichiometry. A portion of the current was Cl- dependent without Cl- cotransport. Most transported monocarboxylates had Km values near 100 µM, with lower affinity observed for acetate and d-lactate. Transport was strongly inhibited by 1 mM probenecid, 1 mM ibuprofen, and prolonged exposure to high substrate concentrations. In the absence of external substrate, a Na+-independent leak current occurred. Transport of monocarboxylate anions was accompanied by intracellular alkalinization.
Why it matters
This study defines the transport function of the tumor suppressor SLC5A8, mechanistically linking its silencing in colon cancer to impaired cellular uptake of growth-inhibiting short-chain fatty acids like butyrate.
Limits
Findings rely on an exogenous heterologous expression system (Xenopus oocytes) rather than human tissue in vivo. The abstract does not report specific sample sizes, confidence intervals, or exact affinity values for individual substrates beyond general approximations.
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