Kalckar completed his medical training at the University of Copenhagen in 1933, and then began research for his Ph. D. in Ejnar Lundsgaard's (1899–1968) physiology laboratory; that work established the foundation of a fundamental biochemical paradigm, i.e. "oxidative phosphorylation". During this period, Lundsgaard was preoccupied as physiology department chair, consequently Fritz Albert Lipmann, who had recently fled Germany, served as Kalckar's research mentor. Later, Kalckar and Lipmann both independently developed concepts of a "high energy bond" (which Lipmann famously expressed as "~P") and ATP as a universal "energy carrier."
Kalckar was fortunate to be working at an important period in biochemistry's evolution. The biochemical community was in the process of demonstrating the chemical reactions involved in breakdown of foodstuffs essential for growth. At the same time, physiologists were demonstrating the involvement of some of these reactions various physiological processes, e.g. muscle contraction. Kalckar's breakthrough work was the demonstration that organic compounds, which were phosphorylated during metabolic processes, involved oxygen consumption; oxygen consumption was linked to organic compound phosphorylation. His key experiment demonstrated that in frog muscles where glycolysis had been inhibited with iodoacetate, muscular contraction continued for a short period using phosphocreatine as a source of energy. Kalckar referred to this process as “aerobic phosphorylation” (now called oxidative phosphorylation, a biochemical process fundamental to all living organisms). The work was the first demonstration that carbohydrate oxidation and carbohydrate phosphorylation were linked, i.e. the two pathways were directly “coupled.” Furthermore, the study helped establish the basic phenomenon of oxidative phosphorylation, opened the way for its systematic exploration, and suggested for the first time that phosphate compounds acted as a link between catabolism and anabolism.
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