Article ID: CBB001320626

Contrasting Approaches to a Biological Problem: Paul Boyer, Peter Mitchell and the Mechanism of the ATP Synthase, 1961--1985 (2013)

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Attempts to solve the puzzling problem of oxidative phosphorylation led to four very different hypotheses each of which suggested a different view of the ATP synthase, the phosphorylating enzyme. During the 1960s and 1970s evidence began to accumulate which rendered Peter Mitchell's chemiosmotic hypothesis, the novel part of which was the proton translocating ATP synthase (ATPase), a plausible explanation. The conformational hypothesis of Paul Boyer implied an enzyme where ATP synthesis was driven by the energy of conformational changes in the respiratory proteins. This was finally abandoned as an explanation of the overall process. Nevertheless the conformational understanding of the enzyme became an acceptable proposal during the early 1970s and eventually led Boyer to a view of the enzyme that incorporated both hypotheses. The correspondence between Mitchell and Boyer, both Nobel laureates, exposes their different approaches to both this enzyme and to the hypotheses of oxidative phosphorylation and illuminates a key step in the development of bioenergetics. In particular Boyer was suspicious of proton gradients, because he could not envisage a chemical mechanism for the synthesis of ATP, while Mitchell distrusted conformational arguments because he believed the proton must act vectorially at the active site of the enzyme. This resulted in two different views of the mechanisms operating in this enzyme. Ultimately while Boyer was able to marry the two approaches, Mitchell retained his insistence on the role of the proton at the active site and was thus unable to give significance to Boyer's conformational ideas. The underlying issues in this debate are discussed particularly with reference to the differing styles of Boyer and Mitchell and the influence of molecular biology, especially the development of protein technology.

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Authors & Contributors
Prebble, John N.
Grote, Mathias
Racine, Valerie
Yi, Doogab
Xiong, Wei-min
Witkowski, Jan A.
Journals
Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences
History and Philosophy of the Life Sciences
Minerva: A Review of Science, Learning and Policy
Journal of the History of Medicine and Allied Sciences
Journal of the History of Biology
Journal of Biosciences
Publishers
Arizona State University
University of Chicago Press
Shandong jiao yu chu ban she
Oxford University Press
Cold Spring Harbor Laboratory Press
Alfred A. Knopf
Concepts
Molecular biology
Biology
Biochemistry
Protein synthesis
Enzymes
DNA; RNA
People
Mitchell, Peter D.
Crick, Francis
Watson, James Dewey
Williams, Robert J. P.
Ochoa, Severo
Monod, Jacques
Time Periods
20th century, late
21st century
Early modern
Modern
20th century, early
20th century
Places
United States
France
Europe
China
Wisconsin (U.S.)
Institutions
The American Society for Cell Biology
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