Submitted on January 23, 2003
Accepted on August 7, 2003
PYRUVATE SHUTTLE IN MUSCLE CELLS : High affinity pyruvate transport sites insensitive to trans-lactate efflux
RAYMOND MENGUAL1*, KAOUAKIB EL ABIDA2, NASSIMA MOUAFFAK2, SOPHIE BUQUOY2, MICHEL RIEU2, and MICHELE BEAUDRY2
1 Institut de Pharmacologie Moleculaire et Cellulaire, CNRS, Sophia Antipolis, Valbonne, France
2 Laboratoire de Physiologie des Adaptations, Universite Rene Descartes, UFR COCHIN PORT ROYAL, Paris, France
* To whom correspondence should be addressed. E-mail: mengual{at}unice.fr.
The specificity of the transport mechanisms for pyruvate and lactate and their sensitivity to inhibitors were studied in L6 skeletal muscle cells. Trans and cis lactate effects on pyruvate transport kinetic parameters were examined. Pyruvate and lactate were transported by a multisite carrier system, i.e. by two families of sites, one with low affinity and high capacity (type I sites) and the other with high affinity and low capacity (type II). The multisite character of transport kinetics was not modified by either hydroxycinnamic acid (CIN) or para-chloromercuribenzylsulfonic acid(PCMBS), which exert different types of inhibition. The transport efficiency ratios Vm/Kt (T.E.) showed that lactate and pyruvate were preferentially transported by type I and II sites, respectively. The cis-lactate effect was observed with high Ki values for both sites. The trans-lactate effect on pyruvate transport occurred only on type I sites and exhibited an asymmetric interaction pattern (KtLACT/in > KtLACT/out). The inability of lactate to trans-stimulate type II sites suggests that intracellular lactate cannot recruit these sites. The high affinity type II sites act as a specific pyruvate shuttle and constitute an essential relay for the intracellular lactate shuttle.
