Molecular cloning of recombinant DNA : proceedings of the Miami winter symposia, January 1977 / edited by W.A. Scott, R. Werner ; sponsored by the Department of Biochemistry, University of Miami, School of Medicine, Miami, Florida.

Date:
1977
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Molecular cloning of recombinant DNA : proceedings of the Miami winter symposia, January 1977 / edited by W.A. Scott, R. Werner ; sponsored by the Department of Biochemistry, University of Miami, School of Medicine, Miami, Florida. Source: Wellcome Collection.

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    4 PAUL BERG and епгзппез to study nucleotide interconversions; Arthur Kornberg lectured on coenzyme structure and biosynthesis, emphasizing mechanisms and the use of enzymes as analytic re¬ agents. I made up my mind then to go to each of their labora¬ tories and learn more about enzymes and nucleotide metabolism. The American Cancer Society was very understanding and pro¬ vided me with a fellowship to spend one year with Kalckar at the Institute of Cytophysiology in Copenhagen and a second year with Kornberg at the NIH. The Old World Experience The year (1952-53) in Copenhagen was idyllic. Now is not the time to reminisce about the innumerable people we met and knew, or of the social and cultural life in that beautiful city. That is for a future occasion. But I would like to recount an interesting bit of history that has never found its way into the scientific literature. When I arrived in Denmark, during October 1952, Herman Kalckar's laboratory was deeply involved with the galacto- waldenase system that Leloir had described a year or two earlier. While the problems that were being investigated interested me, a curious hypothesis by Thomas Rosenberg, a Danish physical chemist friend of Herman's, intrigued me more. Rosenberg suggested that the hexokinase-mediated transphospho- rylation from ATP to glucose formed glucose 6-metaphosphate, which subsequently underwent a spontaneous hydration to form the well known product glucose-6 phosphate (Fig. lA). Rosenberg and Kalckar speculated that the spontaneous (un- catalyzed) hydration of the putative glucose 6-metaphosphate might be rate-limiting; conceivably, they argued, as is the case in the hydration of C02> the conversion of the metaphos- phate intermediate to the glucose phosphomonoester might also be catalyzed and possibly subject to regulation. There was a report that adrenal and pituitary factors as well as insulin affected hexokinase (5). Rosenberg and Kalckar wondered whether these hormones could be acting at the hypothetical glucose-6-metaphosphate hydrase e.g., whether insulin stim¬ ulated this reaction. Since it seemed reasonable that the putative metaphosphate intermediate was high-energy and, therefore, able to react with ADP to reform ATP, I suggested that hexokinase might catalyze a glucose dependent transfer of the terminal phosphate of ATP to IDP (Fig. IB). While I was preparing the labeled reagents and chromato¬ graphic methods to test our proposition. Bill Joklik came to the laboratory after completing his Ph.D. at Oxford, and de¬ cided to join me in testing that outlandish notion. Imagine