Pyruvate shuttle in muscle cells: high-affinity pyruvate transport sites insensitive to trans-lactate efflux

• Published in: American journal of physiology: endocrinology and metabolism 2003-12, Vol.48 (6), p.E1196-E1204
• Main Authors: MENGUAL, Raymond, KAOUKIB EL ABIDA, MOUAFFAK, Nassima, RIEU, Michel, BEAUDRY, Michele
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell division; Fundamental and applied biological sciences. Psychology; Skeletal system; Striated muscle. Tendons; Vertebrates: endocrinology; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0193-1849; 1522-1555

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 p-chloromercuribenzylsulfonic acid (PCMBS), which exert different types of inhibition. The transport efficiency (TE) ratios of maximal velocity to the trans-activation dissociation constant (Kt) showed that lactate and pyruvate were preferentially transported by types 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 (Kt of inward lactate > Kt of outward lactate). 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. [PUBLICATION ABSTRACT]