Résumé
Glutamine (GLN), the most abundant amino acid in plasma, modulates cardiac metabolism, but the underlying mechanism remains unclear. To address this issue, working rat hearts were perfused with 13C‐labeled carbohydrates (CHO) and a long chain fatty acid (oleate) with or without 0.5 mM GLN and 20 ìM azaserine (AZA, an inhibitor of the hexosamine biosynthetic pathway; HBP). GLN increased (1.5‐fold) the contribution of oleate to â‐oxidation (energy) and triglyceride formation (storage). While the former effect was reversed by AZA, both effects were not observed under restricted CHO availability (without pyruvate and insulin). Other data demonstrate that GLN's effects cannot be explained by mechanisms regulating â‐oxidation, namely level of malonyl‐CoA (by HPLC), activity of acetyl‐CoA carboxylase or AMP kinase (by Western). GLN's effects on tissue levels of several metabolites, acetyl‐CoA, succinyl‐CoA and glutamate (unchanged), 2‐ketoglutarate (38% higher; p<0.05) and other Krebs cycle‐related intermediates (citrate, malate and pyruvate: ~20% lower; p<0.05) as well as the labelling of these metabolites from glucose (similar for glutamate, 2KG and citrate indicating marginal 13C dilution) support a minor role of GLN as an energy or anaplerotic substrate. These results reveal an effect of a physiological concentration of GLN on LCFA metabolism via the HBP. (Supported by the FRSQ and CIHR).