Paul Boyer

What Laureates Might Want to Know About the 1997 Chemistry Prize

Tuesday, 30 June 1998
16:00 - 17:00 hrs CEST


Most of the energy derived from the oxygen you consume is used for synthesis of adenosine triphosphate (ATP), by a process called oxidative phosphorylation, that is catalyzed by an enzyme, ATP synthase. The ATP provides energy for a myriad of bodily functions. The presentation will give a chronological sketch covering four decades of research in the field of bioenergetics about how ATP is made. The ATP synthase is a remarkable molecular machine in which an energy-driven rotation of a central inner subunit causes sequential binding changes in three outer catalytic subunits to drive steps in the catalysis. The insights that my research group attained were based to a large extent on measurements of the fate of phosphate oxygens using the heavy isotope 18O, and associated studies with 32P, beginning in the 1950’s. A protein-bound phosphohistidine was discovered, but proved to be an intermediate in a phosphorylation accompanying the citric acid cycle. Observations of the insensitivity of oxygen exchanges to uncouplers of oxidative phosphorylation led to the recongnition that energy is used not primarily to make the ATP molecule but the cause binding changes leading to the release of ATP. Continued occurrence of oxygen exchanges and retention of bound intermediates at low substrate concentrations, together with other observations, showed compulsory participation of multiples catalytic sites. Such participation had not been previously observed with any enzymes. Measurement of the distribution of 18O-isotopomers of ATP or of phosphate formed during synthesis or hydrolysis of ATP showed that all catalytic sites were functioning identically. This led in the early 1980’s to the suggestion of a rotational catalysis in a binding change mechanism. Evidence both supporting and arguing against such catalysis was subsequently presented, and by 1993 perhaps most workers were beginning to accept such a possibility. The presentation of the x-ray structure of the F1-ATPase portion of the synthase by Walker’s group in 1994 dramatically supported the binding change mechanism. Subsequent studies by groups of Junge, Cross and Capaldi demonstrated that a rotation occurred as ATP was hydrolyzed, and in 1997 Yoshida and associates achieved a visual demonstration of rotation by attaching a fluorescently-labeled actin filament to a genetically modified and immobilized ATPase portion of the ATP synthase. Much is yet to be learned about the membrane-bound portion of the synthase that couples the translocation of protons across the membrane to rotation of the inner subunit of the catalytic portion of the enzyme. The gaining of the present insight into how the process of oxidate phosphorylation occurs is regarded as an outstanding achievement in biochemistry for which many investigators deserve credit.

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