Lactate transport is mediated by a membrane-bound carrier in rat skeletal muscle sarcolemmal vesicles.
Level 5 - mechanism / opinion, no new human data
In vitro laboratory study on isolated animal membrane vesicles.
PubMed 2350184 · doi:10.1016/0003-9861(90)90505-s
What was done
Sarcolemmal membrane vesicles were isolated from skeletal muscle of 22 female Sprague-Dawley rats to characterize lactate transport kinetics in an isolated, nonmetabolizing system. Researchers measured L(+)-[U-14C] lactate uptake across 10 concentrations and evaluated temperature sensitivity (37°C vs. 25°C), stereospecificity (L(+) vs. D(-) isomers), competition by other monocarboxylates and metabolites, ion dependence and membrane potentials, and susceptibility to protein-modifying reagents.
What was found
L(+)-lactate transport exhibited saturation kinetics with a Vmax of 139.4 nmol/mg/min and an apparent Km of 40.1 mM. Specific findings include: - Initial uptake of L(+)-lactate was 3-fold higher at 37°C than at 25°C. - D(-)-lactate uptake was linear from 1 to 200 mM, and 1 mM D(-) net uptake was 6-fold lower than L(+) at 60 min; 10 mM unlabeled D(-) inhibited 1 mM L(+) uptake by only 12%. - Unlabeled 10 mM L(+)-lactate and pyruvate inhibited 1 mM L(+)-lactate uptake by 82% and 71%, respectively; beta-hydroxybutyrate and acetoacetate inhibited uptake by 27% and 32%. - Formate, acetate, propionate, TCA cycle intermediates, amino acids, palmitate, and adenosine did not effectively inhibit uptake. - 4,4'-Diisothiocyanostilbene-2,2'-disulfonic acid inhibited uptake by only 13%, and KCl (with or without valinomycin) did not alter uptake, indicating an electroneutral process unaffected by Cl- or HCO3- fluxes. - Protein-modifying agents inhibited transport under pH-stimulated conditions: p-chloromercuriphenyl-sulfonic acid by 83%, N-ethylmaleimide by 86%, HgCl2 by 56%, and mersalyl by 63%.
Why it matters
This study provides direct biochemical evidence that lactate flux across skeletal muscle sarcolemma is mediated by a specific, stereoselective, membrane-bound carrier protein rather than simple passive diffusion.
Limits
The study was performed exclusively in vitro using isolated rat membrane vesicles, which may not fully reflect in vivo transport dynamics or human muscle physiology. Confidence intervals, standard errors, and statistical significance tests were not reported in the abstract.
Cited by
- supports L-lactate uptake shows saturation kinetics, whereas D-lactate uptake is linear and occurs by diffusion without sharing the transporter.
- supports In isolated sarcolemmal vesicles, lactate outcompetes ketones, glucose, and amino acids for transporter uptake because it fits the transporter configuration better.