Monocarboxylate-uptake kinetics in perfused rat heart.
While there is considerable evidence to suggest that lactate and pyruvate transport across the cell membrane is controlled, virtually nothing is known about the mechanisms. To test a prediction that sarcolemmal monocarboxylate transport is mediated by a specific carrier, we have examined the kinetics of pyruvate and lactate uptake into aerobically perfused rat hearts. In preparations depleted of intracellular lactate and pyruvate by a 30-min pre-perfusion in the absence of substrates, various concentrations of [14C]lactate or pyruvate (0.02 Ci/mole), together with [3H]mannitol (50 nCi/ml), were transiently (2 min) infused into the mainstream perfusate immediately above the heart. Uptake was calculated from the difference between the level of 14C-labeled substrate predicted from the extracellular distribution of [3H]mannitol and the actual level (corrected for 14CO2 contamination) measured in successive 20-sec samples of effluent perfusate. Computer optimization analysis of the initially rapid (first 60 sec) uptake rates revealed that monocarboxylate transport is not simply a question of diffusion. On the contrary, the observation of typical saturation kinetics (Vmax 7.7-8.4 mumoles/min per g wet wt.) and cross-inhibition (Ki pyr, 2.3 +/- 0.5 mM; Ki lac, 0.16 +/- 0.02 mM) suggest that transsarcolemmal movement of monocarboxylate may be mediated by a high-affinity lactate (km 3.9 +/- 0.9 mM), low-affinity pyruvate (Km 8.6 +/- 1.1 mM), translocase.
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D008353:Mannitol / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters; D009206:Myocardium / Q000201:enzymology*; D010477:Perfusion; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D012984:Software
D002352:Carrier Proteins; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D011773:Pyruvates; D019344:Lactic Acid; D008353:Mannitol; D019289:Pyruvic Acid