Marie Allen Schroeder1, Helen J. Atherton1,
Philip Lee2, Michael S. Dodd1, Lowri E. Cochlin1,
Kieran E. Clarke1, George K. Radda1,2, Damian J. Tyler1
1Physiology, Anatomy and Genetics,
University of Oxford, Oxford, Oxfordshire, United Kingdom; 2Biomedical
Sciences Institute, Singapore Bioimaging Consortium, Singapore, Singapore
Mitochondrial
acetylcarnitine may be involved in balancing the glucose-fatty acid cycle in
the heart. Here, we used hyperpolarised [2-13C]pyruvate with
magnetic resonance spectroscopy to monitor the incorporation of acetyl-CoA formed
by pyruvate dehydrogenase into the acetylcarnitine pool, and the metabolites
of the Krebs cycle, in real-time and in
vivo. Our results demonstrated that most pyruvate-derived acetyl-CoA
entering the Krebs cycle does not immediately condense with oxaloacetate, but
is first converted to acetylcarnitine. Examination of acetylcarnitine
production from pyruvate-derived acetyl-CoA in vivo revealed that acetylcarnitine provides a rapidly
mobilised mitochondrial buffer for oxidative substrate and may be fundamental
in maintaining high, constant ATP levels in the heart.