The Ukrainian Biochemical Journal (Feb 2020)
The Nobel laureates’ contributions to the study of carbohydrate metabolism and its regulation. A. Harden, H. Euler-Chelpin, C. F. Cori, G. T. Cori, E. Sutherland, L. F. Leloir, H. Krebs, F. Lipmann, P. Mitchell
Abstract
Carbohydrate metabolism is a complex and multi-stage process. Many scientists (biochemists, physiologists, chemists) worked on deciphering this process, but only some of them were awarded the Nobel Prize. Thus, in the early XXth century, the work of A. Garden and H. Euler-Chelpin with yeast cells revealed that the conversion of carbohydrates (sugars) into end products occurs in living cells in several steps with the involvement of enzymes and that this conversion requires the presence of phosphoric acid residue. These studies were the beginning of exploring the chemical reactions (the reactions of intermediate metabolism) that are fundamentals for the vital functions of cells. In 1932, Hans Krebs discovered the ornithine cycle, a sequence of chemical reactions, in which the end product of nitrogen metabolism, urea, is formed in the liver of animals. The apogee of his research was the discovery of tri- and dicarboxylic acid cycle, which combines the oxidation of almost all organic compounds in living organisms. Fritz Lipmann, who in 1945 discovered coenzyme A and identified its role in the activation of organic compounds, furthered the works of H. Krebs. At the time, it became clear how inactive acetic acid and other organic acids are activated in living organisms to be oxidized in the tricarboxylic acid cycle. The great work was done by the spouses Gerty and Carl Cori, and Bernardo Houssay, as well as their students and followers, in particular, Luis Leloir to clarify the mechanism of conversion (synthesis and breakdown) of glycogen in the liver and muscles. The peak of studying the carbohydrate metabolism was the research of Earl Sutherland who in 1958 revealed the regulation of the activity of enzymes involved in the conversion of chemical compounds (the example – phosphorylase), with the participation of the adenylate cyclase enzyme and c-AMP. The discovery of c-AMR established one of the fundamental principles of almost all vital processes. And the culmination of research on carbohydrate metabolism was the unrivaled works of Peter Mitchell, who studied the course of biochemical reactions in cells relative to certain intracellular “landmarks” and who formulated the chemiosmotic theory of oxidative phosphorylation that underlies bioenergetics.
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