Enzyme Regulation: from Allosteric Sites to Intracellular Behavior

Alberto sols, teacher and mentor of spanish biochemists (1917–1989)

“…The high abundance of phosphatases in this tissue appeared to support this view, since they were held responsible for the hydrolysis of the phosphate group incorporated during the transport and phosphorylation process. Sols stated decades later, perhaps with a certain irony, that in his thesis he found “what was expected: an apparent positive correlation” between glucose absorption and alkaline phosphatase content (1). Nevertheless, an interesting outcome of his work during this period was the development of a new method to assay the intestinal absorption of sugars that allowed, by successive observations, “comparative experiments in the same animal and in the same intestinal tract” (2).…”

“…The young Sols developed a curiosity for nature's problems under the influence of his father and of an enthusiastic teacher of natural sciences in school. With chemistry or philosophy appearing as possible professional choices, he decided to go for biology and entered medical school “as the best approximation to it available at the time” (1). He finished his graduate studies in 1944 and, although the teaching of biochemistry had been “very poor,” he joined the group of Ponz and Jiménez‐Vargas in Barcelona to do research for his Ph.D. Thesis on the problem of the mechanism of the intestinal absorption of sugars, a topic that doubtless influenced his future career research.…”

“…The Coris had won the Nobel Prize in 1947 for “their discovery of the course of the catalytic conversion of glycogen” (5) but their research has covered multiple aspects of carbohydrate metabolism. In an unfinished autobiographical chapter, Sols wrote that “the laboratory of Carl and Gerty Cori was at the time the Mecca of metabolic enzymology and Carl had begun his scientific career working on the intestinal absorption of glucose” (1). Witness of the importance of that laboratory is that seven subsequent Nobel Prize‐winners worked there and that in 2004, the American Chemical Society honored the memory of the Coris by naming their former laboratory a National Historic Chemical Landmark.…”

“…The last part of the sentence is likely one of the first mentions, if not the first one, of an allosteric site in an enzyme. The authors did not realize at that moment the great importance of the fact that glucose‐6‐phosphate was the only inhibitor of hexokinase that worked at physiological concentrations thus reinforcing their conclusion of “an intrinsic cellular mechanism for the control of hexokinase reaction.” In his remembrances, Sols lamented not to have discussed more deeply this fact (1). Both he and Crane (10) thought that the unglamorous title of the article, “The noncompetitive inhibition of brain hexokinase by glucose‐6‐phosphate and related compounds,” contributed to the lack of recognition of the importance of their finding.…”

“…Seldom have I aimed for big game. An even when pursuing ordinary prey, I often got distracted shooting at any small fry that came across my way” (1) An interesting reflexion coming from someone who had on his desk the well known Latin sentence Non multa sed multum (not many but much).…”