Membrane Domination of Biological Energy Exchanges: A Message of the 1978 Nobel Award in Chemistry

MEMBRANE DOMINATION OF BIOLOGICAL ENERGY EXCHANGES: A MESSAGE OF THE 1978 NOBEL AWARD IN CHEMISTRY HALVOR N. CHRISTENSEN* I do not assume that Nobel Prizes in any field ordinarily need a Rüssel Lecture to explain them. Nor do I assume that the reader necessarily shares an intense interest in the prize-winning contribution recognized in any given year. Instead, this particular award has a special message that I find worth talking about and that I also find useful for framing some sort of an exposition of what I, along with my research associates, have been trying to accomplish. What intensifies for me the drama of the awarding of the Nobel Prize to Peter Mitchell in 1978 is that the award was made in chemistry, not in that other superficially more plausible complex, loosely titled the Nobel Prize in physiology or medicine. The award was not for a chemical attainment in the usual sense: No new compound was discovered, no definite reaction was interpreted. Instead, what a distinguished group ofchemistsjoined to recognize in Stockholm was the central role of biological membranes in cell energetics, that is, in sustaining concentration gradients and in energetically mediating flows across these membranes—flows that, superficially examined, appear physical. The chemists were the persons to whom the idea must have been most revolutionary, and in no way was this an ingratiating concept to add to chemistry. Perhaps I may say that the award represents a triumph in the recognition of the biophysical over the bioorganic side of chemistry. Our life experiences give us all intuitions about flows, some of them helpful, but some not. Even our helpful analogies prove treacherous. Our familiarity with the milling of people may lead us to accept too easily the "uphill" or against-the-gradient movement of a population of molecules. Biochemists may be more in danger of exchanging their The Henry Rüssel Lecture, University of Michigan, Ann Arbor, March 18, 1980.»Professor of biological chemistry, Medical School, University of Michigan, Ann Arbor, Michigan 48109.© 1981 by The University of Chicago. 0031-5982/81/2403-0235$01.00 358 Halvor N. Christensen ¦ Biological Energy Exchanges sound natural intuitions about flows for dubious learned abstractions about coupling in chemical reactions. The message of the Nobel Prize includes for me an implied criticism of those who leave little room for these flows in their picture of the steady-state functioning of the cell and organelle, those who think only of the regulation ofconcentrations when flows are what ultimately need to be regulated. That is, I believe "homeorhysis," a term generated under advice from Professor Ernst Pulgram, deserves consideration at least parallel to that given homeostasis . The behavior my associates and I have enjoyed studying for some decades is the concentrating of nutrient molecules into cells. This behavior has these molecules moving into the cell interior against a gradient , to a higher concentration than that outside the cell. The nutrient type we chose for study of this phenomenon was one whose metabolism was already of great interest—the amino acids. These molecules, about 20 different ones, are the building stones for the protein molecules, and indeed for our protoplasm. The term "nutrient" tells only part of the story, however, because they are also key intermediates that flow from cell to cell and constitute a traffic which serves for much of the cooperation within the society of cells which each of us represents. Hence it is nutrition at the cellular level that most interests us. Let me use another term, "metabolites," rather than nutrients, to represent this wider scope. It was 30 years ago, at an early stage of this work, that I recall telling a medical school applicant under interview about a discovery we had just made—that in pregnancy the placental membrane separating the mother and the fetus "pumps" the amino acids into the fetal circulation to favor growth of the fetus at the expense of the mother. One never knows what to expect in the background ofan interviewee, but I was still not prepared for his response: "Professor Christensen, didn't you know in advance that it would be so? Why did you think you had to do that research...