Caught in the Middle Between Biology and Medicine: Heart Metabolism in Transition Heinrich Taegtmeyer, MD, DPhil McGovern Medical School at The University of Texas Health Science Center at Houston The history of heart metabolism (Winterstein, 1904) precedes the history of cancer cell metabolism (Warburg, 1924) by a mere two decades. From its outset, cardiac metabolism stresses the need for O2 for the transfer of energy harnessed in substrates to support the heart’s contractile activity. In contrast, from its outset cancer cell metabolism stresses lactate production and cell growth. What cardiologists call “hibernating myocardium” is a sign of tumor growth in glucose-addicted cancers. Undoubtedly, the tracks of oncometabolism are present in the heart, manifesting themselves by a return to the fetal gene program. Rates of energy conversion (or simply the flux of chemical energy to mechanical energy) in the heart are unmatched by other mammalian organs. Conversely, rates of biosynthesis (or simply the energy-consuming flux in and out of all cell constituents) in cancer cells are also unmatched by other mammalian organs. While the complexity of intermediary metabolism is overwhelming, the heart will be introduced as a model system for testing Rudolf Schoenheimer’s hypothesis that “not only the fuel, but also the structural materials are in a steady state of flux” (On the Dynamic State of Body Constituents, 1941). Schoenheimer, who died very young, was the first to use stable isotopes and mass spectroscopy in biological research. I will provide examples in support of the hypothesis that in the stressed heart, metabolic remodeling precedes, triggers, and sustains structural and functional remodeling (Taegtmeyer et al, Ann N Y Acad Sci 2004), and I will conclude with Max Delbrück’s dictum: “The vista of a biochemist is a vista of an infinite horizon” (A physicist looks at biology Trans Conn Acad Sci 1949).
McGovern Medical School at The University of Texas Health Science Center at Houston
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