Carl Cori (1972) - Enzymatic control of glycogen metabolism

Carl Cori (1972)

Enzymatic control of glycogen metabolism

Carl Cori (1972)

Enzymatic control of glycogen metabolism

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Carl Ferdinand Cori was born in Prague in 1896, which was then part of Austria-Hungary. In 1920, he married his wife, Gerta Theresa Cori. Just in the same year, both obtained their MD degrees from the German University of Prague. Two years later, the Coris emigrated to the United States to work as biochemists. Another twenty-five years later, the married couple received a Nobel Prize in Physiology or Medicine and Gerty Cori became the first woman to receive this prize. The two Laureates, who were both originally educated as physicians, were honored for their work in a truly biochemical field: sugar metabolism.The Coris had investigated “the course of the catalytic conversion of glycogen”. Glycogen molecules are very huge molecules (so called macromolecules) built exclusively from glucose subunits. A single glycogen molecule contains tens of thousands of glucose building blocks, which are arranged in branched chains, giving the overall molecule a tree-like structure. Glycogen resembles starch, which is found in plants, differing from it mainly by a higher degree of branching. In the human body, glycogen is used as a means of short-term energy storage. Its build-up and degradation is relatively fast and rapidly regulated. For long-term storage, however, fat is the energy container of choice: a gram of fat stores around six times more bio-accessible energy compared to a gram of glycogen [1]. In the present lecture, Cori gives an exhaustive and rather technical review of the current state of knowledge with regards to glycogen research. He considers the enzymes required for glycogen build-up and degradation as well as their regulation through messenger molecules. In doing so, he also addresses a still highly topical problem in biochemical research: the need for sufficiently simple, but realistic model systems, which allow for the investigation of regulation mechanisms. Such models should ideally make use of intact tissue, Cori says. However, it is naturally a very difficult task to simulate the biochemical conditions inside a living organism with isolated tissue samples. Or, in more technical terms: the extrapolation from in vitro to in vivo conditions is highly prone to systematic errors. Some of the open questions Cori raises during his talk have been answered in the years to come. He explains, for instance, that glycogen is degraded by two enzymes. One of these enzymes, phosphorylase, degrades linear glucose chains, but cannot proceed once it reaches a branching point. Here, it leaves behind a residue of four glucose units. At this point, the second enzyme, the so-called debranching enzyme, resolves the branch, by first transferring three of the four remaining glucose units to another branch (glucosyltransferase activity) and then cleaving the remaining glucose unit (glucosidase activity). Thus a new linear glucose chain is exposed and may be degraded further by phosphorylase. At the time of Cori’s talk, it was not clear whether the debranching enzyme can perform its two functions because it is a single, multifunctional enzyme or because it is actually two enzymes, which could just not be separated yet. From protein structures obtained via x-ray crystallography, we now know, that the answer depends on the organism studied: in mammals and fungi, a single, multifunctional enzyme performs debranching of glycogen. In a number of bacteria, two individual enzymes share the tasks [2].The present lecture is the first of two lectures Cori ever gave in Lindau and the only one dedicated to the area of research that led to the award of the Nobel Prize. In his next lecture, held in 1975, Cori talks about the biochemical consequences of mutations due to radiation in mice. David Siegel[1]B. Alberts et al., Molecular Biology of the Cell, Fifth Edition, 2008, Garland Science, New York, USA. [2]Jespersen et al., Journal of Protein Chemistry, 1993, volume 12, page 791.

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